Oral administration of oligo fucoidan improves the survival rate, quality of life, and immunity in patients with lung cancer.

Background: Lung cancer, the most commonly diagnosed cancer globally, has the highest incidence and mortality rates in Taiwan. It can be divided into two types. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers, which is further divided into adenocarcinoma, squamous cell carcinoma, and large cell lung cancer accounting for approximately 40%, 25%, and 15% of NSCLC cases, respectively. Small cell lung cancer accounts for approximately 15% of lung cancers. Early systemic therapy NSCLC was based on chemotherapy, and immunotherapy is currently under development. Fucoidan, from brown seaweed extracts, shows promise in mitigating radiation-induced lung fibrosis in animal studies, suggesting its potential as an adjuvant for radiation therapy-related lung fibrosis in lung cancer patients. However, the clinical utility of such adjuvant therapy in lung cancer treatment remains uncertain. The purpose of this study was to investigate the effects of oral administration of oligo-fucoidan on the survival rate, quality of life, and immunity of patients with lung cancer. Methods: Subjects with Non-small cell lung cancer aged between 20 and 80 were collected from outpatient clinics, divided into control group (n = 7): conventional therapy and fucoidan group (n = 13): received conventional therapy+ oral supplementation of oligo-fucoidan (550 mg × 4 tablets). Data were collected before the study, at weeks 4, 12, and 24 during the study, and to collect 20 ml of peripheral blood, for analysis biochemical data, liver and kidney function, lymphocyte population, inflammation cytokines, and using EORTC QLQ-C30 questionnaire to assess quality of life. Results: The survival rates of the subjects in the control and fucoidan groups were 20% and 28.6%, respectively. During the study, patients in the fucoidan group experienced a better quality of life than those in the control group, but this difference lacked statistical significance. Oligo-fucoidan increases the CD19 lymphocyte population. The patients in the fucoidan group also had Lower inflammatory cytokine. Conclusion: Oligo-fucoidan holds promise as an adjuvant therapy to enhance the survival rate, quality of life, and immune function in patients with lung cancer.

Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Rapidly reducing cadmium from contaminated farmland soil by novel magnetic recyclable Fe3O4/mercapto-functionalized attapulgite beads.

Reducing cadmium (Cd) content from contaminated farmland soils remains a major challenge due to the difficulty in separating commonly used adsorbents from soils. This study synthesized novel millimeter-sized magnetic Fe3O4/mercapto-functionalized attapulgite beads (MFBs) through a facile one-step gelation process incorporating alginate. The MFBs inherit the environmental stability of alginate and enhance its mechanical strength by hybridizing Fe3O4 and clay mineral components. MFBs can be easily separated from flooded soils by magnets. When applied to 12 Cd-polluted paddy soils and 14 Cd-polluted upland soils, MFBs achieved Cd(II) removal rates ranging from 16.9% to 62.2% and 9.8%-54.6%, respectively, within a 12-h period. The MFBs predominantly targeted the exchangeable and acid soluble, and reducible fractions of Cd, with significantly enhanced removal efficiencies in paddy soils compared to upland soils. Notably, MFBs exhibited superior adsorption performance in soils with lower pH and organic matter (OM) content, where the bioavailability and mobility of Cd are heightened. The reduction of Cd content by MFBs is a sustainable and safe method, as it permanently removes the bioavailable Cd from soil, rather than temporarily reducing its bioavailability. The functional groups such as -SH, -OH, present in attapulgite and alginate of MFBs, played a crucial role in Cd(II) adsorption. Additionally, attapulgite and zeolite provided a porous matrix structure that further enhanced Cd(II) adsorption. The results of X-ray photoelectron spectroscopy suggested that both chemical precipitation and surface complexation contributed to Cd(II) removal. The MFBs maintained 87.6% Cd removal efficiency after 5 regeneration cycles. The surface of the MFBs exposed new adsorption sites and increased the specific surface area during multiple cycles with Cd-contaminated soil. This suggests that MFBs treatment with magnetic retrieval is a potentially effective pathway for the rapid removal of Cd from contaminated farmland soils.

Impacts of simulated atmospheric cadmium deposition on the physiological response and cadmium accumulation of Sedum plumbizincicola.

Atmospheric cadmium (Cd) deposition contributes to the accumulation of Cd in the soil-plant system. Sedum plumbizincicola is a Cd and Zn hyperaccumulator commonly used for the phytoremediation of Cd-contaminated soil. However, studies on the effects of atmospheric Cd deposition on the accumulation of Cd and physiological response in S. plumbizincicola are still limited. A Cd solution spraying pot experiment was conducted with S. plumbizincicola at three atmospheric Cd deposition concentrations (4, 8, and 12 mg/L). Each Cd concentration levels was divided into two groups, non-mulching (foliar-root uptake) and mulching (foliar uptake). The soil type used in the experiment was reddish clayey soil collected from a farmland. The results showed that compared with the non-mulching control, the fresh weight of S. plumbizincicola in non-mulching with high atmospheric Cd deposition (12 mg/L) increased by 11.35%. Compared with those in the control group, the malondialdehyde (MDA) content in the non-mulching and mulching S. plumbizincicola groups increased by 0.88-11.06 nmol/L and 0.96-1.32 nmol/L, respectively. Compared with those in the non-Cd-treated control group, the shoot Cd content in the mulching group significantly increased by 11.09-180.51 mg/kg. Under high Cd depositions, the Cd in S. plumbizincicola mainly originated from the air and was stored in the shoots (39.7-158.5%). These findings highlight that the physiological response and Cd accumulation of S. plumbizincicola were mainly affected by high Cd deposition and suggest that atmospheric Cd could directly be absorbed by S. plumbizincicola. The effect of atmospheric deposition on S. plumbizincicola cannot be ignored.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Combining superpulse dynamic CO2 laser and supramolecular salicylic acid in the treatment of dense comedones with higher clearance in a shorter time: A prospective, randomized, split-face clinical trial.

OBJECTIVES: Dense comedones are common in patients with acne vulgaris, and promoting treatment can prevent the progression of acne lesions. However, the efficacy-time conflict makes the treatment challenging and the medication options are limited by the side effects. MATERIALS AND METHODS: Thirty-five patients with symmetrical dense comedones were enrolled and the two sides of the face were randomly assigned to receive 30% supramolecular salicylic acid (SSA) combined with CO2 laser or CO2 laser monotherapy at an interval of 2 weeks for six treatment sessions. Comedones count, porphyrin index (PI), texture index (TI), melanin index, erythema index, hydration index (HI), transepidermal water loss (TEWL), and side effects were recorded at each visit till the 12th week. RESULTS: Thirty-one patients completed the study. Comedones on the combined-SSA side were reduced more after six treatments, that the mean reduction rate of the combined-SSA side was 85.76%, and that of the CO2 laser-treated side was 62.32% (Pbetween < 0.001). Combining SSA also showed a better effect on reducing PI and TI than CO2 laser singly (Pbetween < 0.001). TEWL and HI between the two sides showed no significant differences after treatments. No permanent or severe side effects were observed on both side. CONCLUSIONS: The treatment combined CO2 laser with 30% SSA dealt with the efficacy-time conflict while significantly reducing comedones and improving skin texture in 12 weeks and no serious adverse reactions occurred. LIMITATIONS: It is a single-center study and the number of subjects was small.

CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

BACKGROUND: The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs. OBJECTIVE: We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs. METHODS: The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments. RESULTS: CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2). CONCLUSIONS: Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.

[Preparation of Iron-modified Biochar and Its Application in Arsenic Contaminated Soil Remediation].

Biochar has a range of advantages including large porosity, high specific surface area, and strong adsorption capacity. It has been widely used in environmental pollution remediation, soil improvement, and carbon sequestration and emission reduction. Arsenic (As) is a highly toxic pollutant widely distributed throughout the soil. In typical surface soils, the most common forms of As are arsenite (AsO33-) and arsenate (AsO43-). Since most biochar surfaces are negatively charged, the adsorption efficiency of biochar to arsenic is usually low, and the biochar material needs to be modified to enhance its As adsorption performance. Iron-based materials, such as zero valent iron and iron oxide, are excellent As adsorption materials with wide environmental sources. They can be loaded to biochar to form iron-modified biochar via precipitation, pyrolysis, ball-milling, and micro-biological methods. The combined advantages of the iron-modified biochar will expand the application of biochar materials in environmental remediation. Based on a systematic analysis of the literature on iron-modified biochar in recent years, this study reviewed the common preparation methods of iron-modified biochars; analyzed biochar substrates, iron-modified biochar, and their synergistic mechanisms on As adsorption; and briefly expounded the application status of iron-modified biochar in soil pollution remediation. The prospects of the future research direction of iron-modified biochar were put forward as a reference for the large-scale application of biochar materials in the future.

Enhanced removal of arsenic and cadmium from contaminated soils using a soluble humic substance coupled with chemical reductant.

Soil washing is an efficient, economical, and green remediation technology for removing several heavy metal (loid)s from contaminated industrial sites. The extraction of green and efficient washing agents from low-cost feedback is crucially important. In this study, a soluble humic substance (HS) extracted from leonardite was first tested to wash soils (red soil, fluvo-aquic soil, and black soil) heavily contaminated with arsenic (As) and cadmium (Cd). A D-optimal mixture design was investigated to optimize the washing parameters. The optimum removal efficiencies of As and Cd by single HS washing were found to be 52.58%-60.20% and 58.52%-86.69%, respectively. Furthermore, a two-step sequential washing with chemical reductant NH2OH•HCl coupled with HS (NH2OH•HCl + HS) was performed to improve the removal efficiency of As and Cd. The two-step sequential washing significantly enhanced the removal of As and Cd to 75.25%-81.53% and 64.53%-97.64%, which makes the residual As and Cd in soil below the risk control standards for construction land. The two-step sequential washing also effectively controlled the mobility and bioavailability of residual As and Cd. However, the activities of soil catalase and urease significantly decreased after the NH2OH•HCl + HS washing. Follow-up measures such as soil neutralization could be applied to relieve and restore the soil enzyme activity. In general, the two-step sequential soil washing with NH2OH•HCl + HS is a fast and efficient method for simultaneously removing high content of As and Cd from contaminated soils.

Accumulation of advanced oxidation protein products contributes to age-related impairment of gap junction intercellular communication in osteocytes of male mice.

AIMS: Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes' GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes' GJIC in aged male mice and its mechanism. METHODS: Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. RESULTS: The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes' GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. CONCLUSION: Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413-425.

Enhancing effects of dissolved and media surface-bound organic matter on titanium dioxide nanoparticles transport in iron oxide-coated porous media under acidic conditions.

Natural organic matter (NOM) and iron oxides have been proved to be crucial factors controlling the behaviors of nanoparticles in heterogenous environment. Here, we conducted experimental and modeling study on the transport of titanium dioxide nanoparticles (TiO2 NPs) in iron oxide-coated quartz in the presence of NOM under acidic conditions. Results showed the antagonistic effects of iron oxides and NOM on TiO2 NPs mobility. The inhibition of iron oxides coated on quartz was crystal form-dependent other than quantity-dependent. Amorphous ferric oxyhydroxide with higher specific surface area brought more positive charge and favorable deposition sites onto quartz, and induced more retention of nanoparticles than two crystalline iron oxides, goethite and hematite. Dissolved organic matter (DOM) facilitated TiO2 NPs transport in iron oxide-coated quartz. In comparation with the limited enhancing effects of DOM, the NOM coatings on media surface partially or largely offset the inhibition of goethite on nanoparticles mobility through direct occupation of attachment sites and sites screening due to the steric repulsion of the macromolecules. Owing to the higher steric hindrance, humic acid, both in dissolved and media surface-bound states, exerted stronger facilitating effects on TiO2 NPs mobility relative to fulvic acid.

Effects of land use and landscape on the occurrence and distribution of microplastics in soil, China.

Microplastic pollution in the soil environment has gathered widespread attention. However, little is known about the effects of land use and landscape patterns on the occurrence and distribution of microplastics in the soil. Herein, the microplastic pollution in different land uses (facility farmland, traditional farmland, orchard, grassland, and woodland) in Yuanmou County, Yunnan Province was investigated. The results showed that the abundance of microplastic ranged from 50.000 to 3450.0 items·kg-1, with an average abundance of 595.00 ± 740.00 items·kg-1 and a median of 375.00 items·kg-1. Microplastics were found to primarily be green-coloured (28.4 %), fragment (72.7 %) in shape, <1 mm (75.7 %) in size, and composed of polypropylene (51.4 %). There were significant differences in the abundance and characteristics of the microplastics between different land use types. Microplastic abundance in facility farmlands, traditional farmlands, and orchard lands was significantly higher than that of grasslands and woodlands (p < 0.05). The main shape of the microplastics in facility farmlands, traditional farmlands, and orchards was fragments and it was fibers in grasslands and woodlands. The median particle size of microplastics in facility farmlands (539.50 µm) and traditional farmlands (574.00 µm), was smaller than those in the orchard (737.60 µm), grasslands (697.60 µm), and woodlands (1239.4 µm). Discrepancies among different land uses may be due to various reasons, such as different pollution sources and the weathering degree of microplastics. The results of the redundancy analysis showed that the microplastic abundance was negatively correlated with the largest patch index. It also showed that microplastic pollution was closely related to human activities. This study provides an important basis for further research on microplastic ecosystem risks that are associated with land use and provides a data basis for formulating effective prevention and control strategies and measures to mitigate soil microplastic pollution.

Responses of Labile Organic Carbon and Extractable Cadmium Fractions in an Agricultural Soil Following Long-Term Repeated Application of Pig Manure and Effective Microbes.

Long-term pig manure addition has been widely applied in red soil to improve soil fertility. However, the influence of combined utilization of pig manure and effective microbes (EM) on soil organic carbon (SOC) and Cd are not well understood. This study conducted a 23-year (1996-2019) long-term fertilization field trial to investigate the changes of different fractions of SOC and Cd under chemical fertilization (CF), pig manure (PM), and pig manure with effective microbes (PM + EM) treatments in an agricultural soil of Jiangxi Province, South China. The results showed that the pig manure addition significantly enhanced the contents of SOC and Cd in the soils compared with the CF treatments. Furthermore, with the increment of SOC, the PM + EM treatment significantly increased the contents of soil microbial biomass carbon, dissolved organic carbon and easily oxidizable carbon compared with the pig manure application alone. Meanwhile, compared with the CF treatments, the EM addition significantly enhanced the exchangeable and oxidizable fractions of Cd, thus the potential Cd environment risk due to pig manure application should be carefully assessed.

Carbon ion radiotherapy triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy in mice.

Carbon ion radiotherapy (CIRT) is an emerging type of radiotherapy for the treatment of solid tumors. In recent years, evidence accumulated that CIRT improves the therapeutic outcome in patients with otherwise poor response to immune checkpoint blockade. Here, we aimed at identifying the underlying mechanisms of CIRT-induced tumor immunogenicity and treatment efficacy. We used human U2OS osteosarcoma cells for the in vitro assessment of immunogenic cell death and established several in vivo models of melanoma in mice. We treated the animals with conventional radiation, CIRT, PD-1-targeting immune checkpoint blockade or a sequential combinations of radiotherapy with checkpoint blockade. We utilized flow cytometry, polyacrylamide gel electrophoresis (PAGE) and immunoblot analysis, immunofluorescence, immunohistochemistry, as well as enzyme-linked immunosorbent assays (ELISA) to assess biomarkers of immunogenic cell death in vitro. Treatment efficacy was studied by tumor growth assessment and the tumor immune infiltrate was analyzed by flow cytometry and immunohistochemistry. Compared with conventional radioimmunotherapy, the combination of CIRT with anti-PD-1 more efficiently triggered traits of immunogenic cell death including the exposure of calreticulin, the release of adenosine triphosphate (ATP), the exodus of high-mobility group box 1 (HMGB1) as well as the induction of type-1 interferon responses. In addition, CIRT plus anti-PD-1 led to an increased infiltration of CD4+, and CD8+ lymphocytes into the tumor bed, significantly decreased tumor growth and prolonged survival of melanoma bearing mice. We herein provide evidence that CIRT-triggered immunogenic cell death, enhanced tumor immunogenicity and improved the efficacy of subsequent anti-PD-1 immunotherapy.

Age-related accumulation of advanced oxidation protein products promotes osteoclastogenesis through disruption of redox homeostasis.

Enhanced osteoclastogenesis is one of the major causes of age-related bone loss. Aging is accompanied by accumulation of advanced oxidation protein products (AOPPs). However, whether AOPPs accumulation contributing to the osteoclastogenesis with aging remains unclear. Here, we showed that AOPPs accumulation was associated with the enhanced osteoclastogenesis and deterioration of bone microstructure in aged mice. In vitro, AOPPs directly induced osteoclastogenesis by interaction with receptor activator of nuclear factor κ B (RANK) and the receptor for advanced glycation end products (RAGE) in the primary bone marrow monocytes. Bindings of AOPPs to RANK and RAGE were able to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, trigger generation of reactive oxygen species, then induce phosphorylation of mitogen-activated protein kinases and c-fos, upregulation of the nuclear factor of activated T cell c1, eventually induce bone marrow monocytes to differentiate into mature osteoclasts. Chronic exposure to AOPPs enhanced osteoclastogenesis and bone loss in mice, which could be alleviated by NADPH oxidase inhibitor apocynin. Local injection of AOPPs into subperiosteal area induced bone resorption at the site of administration, which was similar to the effect of RANK ligand. Together, these results suggested that AOPPs could serve as a novel regulator of osteoclastogenesis and AOPPs accumulation might play an important role in the development of age-related bone loss.

Microplastics in an agricultural soil following repeated application of three types of sewage sludge: A field study.

Microplastics were investigated in an agricultural soil to which three types of sludge were repeatedly applied: fresh municipal sludge (FSS1), fresh mixed sludge (mainly industrial sludge) (FSS2), and dry heat-treated municipal sludge (DSS). The percentages of microplastics <1.0 mm were 24.3 and 28.7-59.1 % in unamended and amended soils, respectively. Particles of this size accounted for 47.1-60.0 % of microplastics in different sludges and polymers of particle size <100 µm occurred in all soil samples and sludges examined. Fibers were the commonest microplastic type, ranging from 66.7 to 82.5 % in soil and 89.4-97.2 % in sludges. Polyester (PES) and polypropylene (PP) accounted for ~80 % of the total microplastics found in soil and poly-(styrene:acrylate) (PS-AC) microspheres were found in all sludge-amended soil samples examined. There was also a pronounced weathering effect on the surfaces of the microplastics in soil. Nine years of repeated sludge application led to the accumulation of microplastics in the soil. The abundance of microplastics was significantly higher in the municipal sludge (149.2 ± 52.5 particles kg-1) than in the mixed (68.6 ± 21.5 particles kg-1) or dried (73.1 ± 15.4 particles kg-1) sludge and this was related to the microplastic abundance in the sludges. This field study confirms that sludges are drivers of soil microplastic pollution and measures are required to minimize the inputs of microplastics to agricultural land.

Structural and Functional Characteristics of Microplastic Associated Biofilms in Response to Temporal Dynamics and Polymer Types.

The colonization of bacterial communities and biofilm formation on microplastics (MPs) have aroused great concern recently. However, the influence of time and polymer types on the structural and functional characteristics of biofilms remains unclear. In this study, three types of MPs (polyethylene, polypropylene, and polystyrene) were exposed for different time periods (10, 20 and 30 days) in seawater using a microcosm experiment. Microscopic spectroscopy and high-throughput gene sequencing techniques were used to reveal the temporal changes of structural and functional characteristics of MPs associated biofilms. The results indicate that the biofilm formation is affected by both the incubation time and the polymer type. In addition, bacterial diversity and community structure in the biofilms show selectivity towards seawater, and tend to shift over time and among different polymer types. Moreover, biofilms are shown to harbor plastic degrading bacteria, leading to the changes of functional groups and surface hydrophobicity, and thereby enhancing the biodegradation of MPs.

Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan.

Non-small cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common histopathological subtype. Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR tyrosine kinase inhibitors. Interleukin (IL)-17A secreted by T-helper 17 lymphocytes is a proinflammatory cytokine that plays an important role in cancer pathogenesis. The present study was designed to investigate the possible associations among IL-17A genetic polymorphisms, EGFR mutation status, and the clinicopathologic development of LUAD in a Taiwanese population. Our study population consisted of 277 LUAD patients harboring the wild-type (WT) EGFR or a mutant (MT) EGFR. Four single-nucleotide polymorphisms (SNPs) of IL-17A in the peripheral blood, including rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, were genotyped using a TaqMan allelic discrimination assay. Our results showed that none of these IL-17A SNPs were correlated with the risk of developing mutant EGFR. However, patients with a smoking habit who carried the GA genotype of IL-17A rs8193037 had a significantly lower susceptibility to EGFR mutations (adjusted odds ratio (AOR): 0.225; 95% confidence interval (CI): 0.056~0.900, p = 0.035). Moreover, compared to individuals carrying the CC genotype of rs8193036 at IL-17A, T-allele carriers (CT + TT) were at higher risk of developing more-advanced stages (stage III or IV; p = 0.020). In the WT EGFR subgroup analysis, IL-17A rs8193036 T-allele carriers had higher risks of developing an advanced tumor stage (p = 0.016) and lymphatic invasion (p = 0.049). Further analyses of clinical datasets revealed correlations of IL-17 receptor A (IL-17RA) and IL-17RC expressions with a poor prognosis of LUAD patients with a smoking history or with higher levels of tumor-infiltrating lymphocytes. In conclusion, our results suggested that two functional promoter polymorphisms of IL-17A, i.e., rs8193036 and rs8193037, were associated with the EGFR mutation status and progression in LUAD patients, indicating that these two genetic variants might act as possible markers for predicting patients' clinical prognoses.

Lead smelting alters wheat flour heavy metal concentrations and health risks.

Wheat (Triticum aestivum L.) flour consumption may be a major source of human metal intake, especially when wheat is cultivated in metal-contaminated soils. This work investigated Cd, Cu, Pb, and Zn distribution in whole wheat flour, wheat flour, and wheat bran when grown in an area polluted by Pb smelting. Wheat product heavy metal concentrations were analyzed, and the (non)carcinogenic risks were assessed. Mean Cd, Cu, Pb, and Zn concentrations in whole wheat flour were 0.38, 3.83, 0.48, and 29.3 mg kg-1 , respectively; those in flour were only slightly reduced. The ratios between noncarcinogenic average daily dose of whole wheat flour and wheat flour consumption ranged from 1.06 to 3.76, with Pb having the greatest values compared with other metals. For children, the average hazard quotients (HQs) of whole wheat flour consumption of Cd, Cu, Pb, and Zn were 4.19, 1.06, 1.53, and 1.07; those for wheat flour consumption were 3.81, 0.68, 0.70, and 0.98, respectively. The HQs of adults were less than those of children. Overall results indicated that consumption of wheat products may lead to health concerns in the heavy metal contaminated area, yet when wheat flour rather than whole wheat flour is consumed, only the human health risk from Pb ingestion is reduced. Altering or removing human edible crops in the most contaminated areas should be considered.

FUT8 Remodeling of EGFR Regulates Epidermal Keratinocyte Proliferation during Psoriasis Development.

α-(1,6)-fucosyltransferase 8 (FUT8) is implicated in the pathogenesis of several malignancies, but its role in psoriasis is poorly understood. In this study, we show that FUT8 remodeling of EGFR plays a critical role in the development of psoriasis phenotypes. Notably, elevated FUT8 expression was associated with disease severity in the lesional epidermis of a patient with psoriasis. FUT8 gain of function promoted HaCaT cell proliferation, whereas short hairpin FUT8 reduced cell proliferation and induced a longer S phase with downregulation of cyclin A1 expression. Furthermore, cell proliferation, which is controlled by the activation of EGFR, was shown to be regulated by FUT8 core fucosylation of EGFR. Short hairpin FUT8 significantly reduced EGFR/protein kinase B signaling and slowed EGF‒EGFR complex trafficking to the perinuclear region. Moreover, short hairpin FUT8 reduced ligand-induced EGFR dimerization. Overactivated EGFR was observed in the lesional epidermis of both human patient and psoriasis-like mouse model, whereas conditional knockout of FUT8 in an IL-23 psoriasis-like mouse model ameliorated disease phenotypes and reduced EGFR activation in the epidermis. These findings implied that elevated FUT8 expression in the lesional epidermis is implicated in the development of psoriasis phenotypes, being required for EGFR overactivation and leading to keratinocyte hyperproliferation.