Short-term microplastic effects on marine meiofauna abundance, diversity and community composition.

Background: Due to the copious disposal of plastics, marine ecosystems receive a large part of this waste. Microplastics (MPs) are solid particles smaller than 5 millimeters in size. Among the plastic polymers, polystyrene (PS) is one of the most commonly used and discarded. Due to its density being greater than that of water, it accumulates in marine sediments, potentially affecting benthic communities. This study investigated the ingestion of MP and their effect on the meiofauna community of a sandy beach. Meiofauna are an important trophic link between the basal and higher trophic levels of sedimentary food webs and may therefore be substantially involved in trophic transfer of MP and their associated compounds. Methods: We incubated microcosms without addition of MP (controls) and treatments contaminated with PS MP (1-µm) in marine sediments at three nominal concentrations (103, 105, 107particles/mL), for nine days, and sampled for meiofauna with collections every three days. At each sampling time, meiofauna were collected, quantified and identified to higher-taxon level, and ingestion of MP was quantified under an epifluorescence microscope. Results: Except for Tardigrada, all meiofauna taxa (Nematoda, turbellarians, Copepoda, Nauplii, Acari and Gastrotricha) ingested MP. Absorption was strongly dose dependent, being highest at 107 particles/mL, very low at 105 particles/mL and non-demonstrable at 103 particles/mL. Nematodes accumulated MP mainly in the intestine; MP abundance in the intestine increased with increasing incubation time. The total meiofauna density and species richness were significantly lower at the lowest MP concentration, while at the highest concentration these parameters were very similar to the control. In contrast, Shannon-Wiener diversity and evenness were greater in treatments with low MP concentration. However, these results should be interpreted with caution because of the low meiofauna abundances at the lower two MP concentrations. Conclusion: At the highest MP concentration, abundance, taxonomic diversity and community structure of a beach meiofauna community were not significantly affected, suggesting that MP effects on meiofauna are at most subtle. However, lower MP concentrations did cause substantial declines in abundance and diversity, in line with previous studies at the population and community level. While we can only speculate on the underlying mechanism(s) of this counterintuitive response, results suggest that further research is needed to better understand MP effects on marine benthic communities.

Dose-dependent effects of polystyrene nanoplastics on growth, photosynthesis, and astaxanthin synthesis in Haematococcus pluvialis.

Microalgae play an important role in aquatic ecosystems, but the widespread presence of micro- and nano-plastics (MNPs) poses significant threats to them. Haematococcus pluvialis is well-known for its ability to produce the antioxidant astaxanthin when it experiences stress from environmental conditions. Here we examined the effects of polystyrene nanoplastics (PS-NPs) at concentrations of 0.1, 1, and 10 mg/L on H. pluvialis over an 18-day period. Our results show that PS-NPs caused a significant, dose-dependent inhibition of H. pluvialis growth and a reduction in photosynthesis. Furthermore, PS-NPs severely damaged the morphology of H. pluvialis, leading to cell shrinkage, collapse, content release, and aggregation. Additionally, PS-NPs induced a dose-dependent increase in soluble protein content and a decrease in the production of extracellular polymeric substances. These findings indicate that PS-NPs has the potential to adversely affect both the physiology and morphology of H. pluvialis. An increase in reactive oxygen species and antioxidant enzyme activities was also observed, suggesting an oxidative stress response to PS-NPs exposure. Notably, the synthesis of astaxanthin, which is crucial for H. pluvialis's survival under stress, was significantly inhibited in a dose-dependent manner under strong light conditions, along with the down-regulation of genes involved in the astaxanthin biosynthesis pathway. This suggests that PS-NPs exposure reduces H. pluvialis's ability to survive under adverse conditions. This study enhances our understanding of the toxic effects of PS-NPs on microalgae and underscores the urgent need for measures to mitigate MNP pollution to protect aquatic ecosystems.

Dose Consideration of Lenvatinib's Anti-Cancer Effect on Hepatocellular Carcinoma and the Potential Benefit of Combined Colchicine Therapy.

PURPOSE: The dose-dependent anti-cancer effect of lenvatinib on hepatocellular carcinoma (HCC) cells and the potential benefit of combined colchicine therapy were investigated. METHODS: Four primary cultured HCC (S103, S143, S160, S176) cell lines were investigated by differential expressions of genes (11 lenvatinib target genes and NANOG) and anti-proliferative effect using clinically achievable plasma lenvatinib (250, 350 ng/mL) and colchicine (4 ng/mL) concentrations. RESULTS: Colchicine showed an anti-proliferative effect on all cell lines. Lenvatinib at 250 ng/mL inhibited proliferation in all cell lines, but 350 ng/mL inhibited only three cell lines. For lenvatinib target genes, colchicine down-regulated more genes and up-regulated less genes than lenvatinib did in three cell lines. Lenvatinib up-regulated NANOG in all cell lines. Colchicine down-regulated NANOG in three cell lines but up-regulated NANOG with less magnitude than lenvatinib did in S103. Overall, combined colchicine and 250 ng/mL lenvatinib had the best anti-cancer effects in S143, with similar effects with combined colchicine and 350 ng/mL lenvatinib in S176 but less effects than combined colchicine and 350 ng/mL lenvatinib in S103 and S160. CONCLUSIONS: Lenvatinib does not show a dose-dependent anti-cancer effect on HCC. Combined colchicine and lenvatinib can promote the total anti-cancer effects on HCC.

Dose-related effects of early-life intake of sn-2 palmitate, a specific positionally distributed human milk fatty acid, on the composition and metabolism of the intestinal microbiota.

sn2 Palmitate in human milk plays an important role in the physiological health of infants by reducing mineral loss, improving stool hardness, and relieving constipation. Also, sn-2 palmitate modulates intestinal microbiota. However, it remains unclear whether the effects of sn-2 palmitate on infant gut microbiota are dose-dependent. In this study, we investigated the effects of low, medium, and high doses (600, 1,800, and 5,400 mg/kg body weight, respectively) of sn-2 palmitate on the structure, composition, and metabolic function of intestinal microbes in mice. Our results showed that high doses of sn-2 palmitate significantly modulated α- and ß-diversity of the intestinal microbiota. The relative abundance of Lachnospiraceae_NK4A136_group decreased with increasing doses of sn-2 palmitate. In contrast, the abundances of Bacteroidetes phylum, Bacteroides, uncultured_Lachnospiraceae, and uncultured_Muribaculaceae were positively correlated with sn-2 palmitate doses. The number of genes predicted encoding autophagy-yeast, phospholipase D signaling pathway, and pentose and glucuronate interconversion metabolic functions of intestinal microbiota increased with increasing doses of sn-2 palmitate. In addition, low and medium doses of sn-2 palmitate significantly upregulated the arginine and proline metabolic pathways, and high doses of sn-2 palmitate significantly increased purine metabolism. Our results revealed that the effects of sn-2 palmitate intake early in life on the composition and metabolism of the intestinal microbiota of mice showed dose-related differences. The study is expected to provide a scientific basis for the development of infant formulas.

How to perceive the insecticide? The Neotropical termite Nasutitermes corniger (Termitidae: Nasutitermitinae) triggers alert behavior after exposure to imidacloprid.

In eusocial insects, alarm signaling is used to inform nestmates about threats such as predators, competitors, and pathogens. Such behavior is important for the survival of colonies. However, studies evaluating the effect of insecticides on the alarm in termites have not yet been reported. Here, we inspected the effects of insecticide on alarm communication in Nasutitermes corniger. Specifically, we test the following hypotheses: (1) termite groups exposed to insecticide imidacloprid increase the body shaking movements, displaying an alert behavior; and (2) the alert behavior displayed after exposition to insecticide is dose dependent. Bioassays were conducted evaluating the body shaking movements and walking activity of termite groups exposed and non-exposed to insecticide. Thereafter, body shaking movements were evaluated in groups submitted to different doses of insecticide. In general, exposing termite groups to insecticide resulted in significantly higher body shaking movements compared to non-exposed groups. There was a positive effect of imidacloprid doses on the shaking movements. Walking activity, however, decreases in those groups exposed to the insecticide. Our results demonstrate the existence of 'insecticide alert behavior' in N. corniger and it appears to be a previously unrecognized communication mechanism in termites that allows for reducing the intoxication risks in the colony.

Thyroid autoimmunity and adverse pregnancy outcomes: A multiple center retrospective study.

Background: The relationship between thyroid autoimmunity (TAI) and adverse pregnancy outcomes is disputable, and their dose-dependent association have not been fully clarified. Objective: To investigate the association and dose-dependent effect of TAI with multiple maternal and fetal-neonatal complications. Methods: This study is a multi-center retrospective cohort study based on singleton pregnancies of three medical college hospitals from July 2013 to October 2021. The evolution of thyroid function parameters in TAI and not TAI women were described, throughout pregnancy. The prevalences of maternal and fetal-neonatal complications were compared between the TAI and control group. Logistic regression was performed to study the risk effects and dose-dependent effects of thyroid autoantibodies on pregnancy complications, with adjustment of maternal age, BMI, gravidity, TSH concentrations, FT4 concentrations and history of infertility. Results: A total of 27408 participants were included in final analysis, with 5342 (19.49%) in the TAI group and 22066 (80.51%) in control group. TSH concentrations was higher in TAI women in baseline and remain higher before the third trimester. Positive thyroid autoantibodies were independently associated with higher risk of pregnancy-induced hypertension (OR: 1.215, 95%CI: 1.026-1.439), gestational diabetes mellitus (OR: 1.088, 95%CI: 1.001-1.183), and neonatal admission to NICU (OR: 1.084, 95%CI: 1.004-1.171). Quantitative analysis showed that increasing TPOAb concentration was correlated with higher probability of pregnancy-induced hypertension, and increasing TGAb concentration was positively correlated with pregnancy-induced hypertension, small for gestational age and NICU admission. Both TPOAb and TGAb concentration were negatively associated with neonatal birthweight. Conclusion: Thyroid autoimmunity is independently associated with pregnancy-induced hypertension, gestational diabetes mellitus, neonatal lower birthweight and admission to NICU. Dose-dependent association were found between TPOAb and pregnancy-induced hypertension, and between TGAb and pregnancy-induced hypertension, small for gestational age and NICU admission.

The dose-dependent effect of 1.5-GHz microwave exposure on spatial memory and the NMDAR pathway in Wistar rats.

A certain power of microwave radiation could cause changes in the nervous, cardiovascular, and other systems of the body, and the brain was a sensitive target organ of microwave radiation injury. Studies have shown that microwaves can impair cognitive functions in humans and animals, such as learning and memory, attention, and orientation. The dose-dependent effect of microwave radiation is still unclear. Our study aimed to investigate the effects of 1.5-GHz microwaves with different average power densities on locative learning and memory abilities, hippocampal structure, and related N-methyl D-aspartate receptor (NMDAR) signalling pathway proteins in rats. A total number of 140 male Wistar rats were randomly divided into four groups: S group (sham exposure), L5 group (1.5-GHz microwaves with average power density = 5 mW/cm2), L30 group (1.5-GHz microwaves with average power density = 30 mW/cm2), and L50 group (1.5-GHz microwaves with average power density = 50 mW/cm2). Changes in spatial learning and memory, EEG activity, hippocampal structure, and NMDAR signalling pathway molecules were detected from 6 h to 28 d after microwave exposure. After exposure to 1.5-GHz microwaves, rats in the L30 and L50 groups showed impaired spatial memory, inhibited EEG activity, pyknosis and hyperchromatism of neuron nucleus, and changes in NMDAR subunits and downstream signalling molecules. In conclusion, 1.5-GHz microwaves with an average power density of 5, 30, and 50 mW/cm2 could induce spatial memory dysfunction, hippocampal structure changes, and changes in protein levels in rats, and there was a defined dose-dependent effect.

Dose-Dependent Effects of Radiation on Mitochondrial Morphology and Clonogenic Cell Survival in Human Microvascular Endothelial Cells.

To better understand radiation-induced organ dysfunction at both high and low doses, it is critical to understand how endothelial cells (ECs) respond to radiation. The impact of irradiation (IR) on ECs varies depending on the dose administered. High doses can directly damage ECs, leading to EC impairment. In contrast, the effects of low doses on ECs are subtle but more complex. Low doses in this study refer to radiation exposure levels that are below those that cause immediate and necrotic damage. Mitochondria are the primary cellular components affected by IR, and this study explored their role in determining the effect of radiation on microvascular endothelial cells. Human dermal microvascular ECs (HMEC-1) were exposed to varying IR doses ranging from 0.1 Gy to 8 Gy (~0.4 Gy/min) in the AFRRI 60-Cobalt facility. Results indicated that high doses led to a dose-dependent reduction in cell survival, which can be attributed to factors such as DNA damage, oxidative stress, cell senescence, and mitochondrial dysfunction. However, low doses induced a small but significant increase in cell survival, and this was achieved without detectable DNA damage, oxidative stress, cell senescence, or mitochondrial dysfunction in HMEC-1. Moreover, the mitochondrial morphology was assessed, revealing that all doses increased the percentage of elongated mitochondria, with low doses (0.25 Gy and 0.5 Gy) having a greater effect than high doses. However, only high doses caused an increase in mitochondrial fragmentation/swelling. The study further revealed that low doses induced mitochondrial elongation, likely via an increase in mitochondrial fusion protein 1 (Mfn1), while high doses caused mitochondrial fragmentation via a decrease in optic atrophy protein 1 (Opa1). In conclusion, the study suggests, for the first time, that changes in mitochondrial morphology are likely involved in the mechanism for the radiation dose-dependent effect on the survival of microvascular endothelial cells. This research, by delineating the specific mechanisms through which radiation affects endothelial cells, offers invaluable insights into the potential impact of radiation exposure on cardiovascular health.

The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies.

The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.

Evaluation of Multivalent Enterotoxigenic Escherichia coli Vaccine Candidate MecVax Antigen Dose-Dependent Effect in a Murine Model.

There are no licensed vaccines against enterotoxigenic Escherichia coli (ETEC), a leading cause of children's diarrhea and travelers' diarrhea. Recently, protein-based vaccine candidate MecVax was demonstrated to induce functional antibodies against both ETEC toxins (heat-stable toxin [STa] and heat-labile toxin [LT]) and seven ETEC adhesins (CFA/I and CS1 to CS6) and to protect against ETEC clinical diarrhea or intestinal colonization preclinically. Those studies used intraperitoneal, intramuscular, and intradermal routes, and a dose range for MecVax protein antigens, toxoid fusion 3xSTaN12S-mnLTR192G/L211A, and adhesin CFA/I/II/IV MEFA has not been investigated. Here, we further characterized MecVax broad immunogenicity, utilizing a subcutaneous route, and examined vaccine dose-dependent antibody response effects and also antibody functional activities against ETEC enterotoxicity and bacterial adherence. Data showed that mice immunized subcutaneously with MecVax developed robust IgG responses to seven ETEC adhesins (CFA/I, as well as CS1 to CS6) and two toxins (STa and LT). At a subcutaneous dose of 25, 20, or 10 µg or at an intramuscular dose of 12, 6, or 3 µg, MecVax induced similar levels IgG responses to the targeted toxins and adhesins, and these antibodies exhibited equivalent functional activities against ETEC toxin enterotoxicity and bacterial adherence. Once the intramuscular dose was decreased to 1 µg, vaccine-induced antibodies were significantly reduced and no longer neutralized STa enterotoxicity. The results indicated that MecVax administered subcutaneously is broadly immunogenic and, at an intramuscular dose of 3 µg, can induce functional antitoxin and anti-adhesin antibodies in mice, providing instructive information for future vaccine dose studies in humans and accelerating MecVax vaccine development. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) is a leading cause of children's diarrhea and the most common cause of travelers' diarrhea. ETEC infections are responsible for >200 million diarrhea clinical cases and near 100,000 deaths annually. Currently, there are no licensed vaccines for ETEC diarrhea. The protein-based vaccine candidate MecVax unprecedentedly targets two ETEC toxins (STa and LT, produced by all ETEC strains) and seven ETEC adhesins (CFA/I, as well as CS1 to CS6, associated with >60% of ETEC clinical diarrhea cases) and has been demonstrated to be broadly immunogenic and cross protective; as such, it represents a potentially effective multivalent vaccine against ETEC-associated children's and travelers' diarrhea. This study further confirmed MecVax broad immunogenicity and evaluated the vaccine antigen dose effect on the induction of antigen-specific antibody responses in mice and on antibody functional activities against ETEC toxin enterotoxicity and bacterial adherence, yielding useful information for future human volunteer studies and the development of MecVax as an effective ETEC vaccine.

Current Advances in Structure-Function Relationships and Dose-Dependent Effects of Human Milk Oligosaccharides.

HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, HMOs play an important role in regulating neonatal intestinal immunity, resisting viral and bacterial infections, displaying anti-inflammatory characteristics, and promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing the structure-activity relationships and dose-dependent effects of HMOs is lacking. Hence, after introducing the structures and synthetic pathways of HMOs, this review summarizes and categorizes identified structure-function relationships of HMOs. Differential mechanisms of different structural HMOs utilization by microorganisms are summarized. This review also emphasizes the recent advances in the interactions between different health benefits and the variance of dosage effect based on in vitro cell tests, animal experiments, and human intervention studies. The potential relationships between the chemical structure, the dosage selection, and the physiological properties of HMOs as functional foods are vital for further understanding of HMOs and their future applications.

Effects of renin-angiotensin system inhibitor type and dosage on survival after transcatheter aortic valve implantation.

AIMS: The objective of the study was to determine the effect of renin-angiotensin system inhibitors (RASI) on the survival of subgroups of patients with aortic stenosis after transcatheter aortic valve implantation (TAVI) and to assess the impact of types and dosages of RASI on outcomes. METHODS AND RESULTS: This single-centre, retrospective analysis included 2862 patients (n = 2227 with RASI and n = 635 without RASI) after successful TAVI. Propensity score matching established comparable patient populations (n = 625 per group). Survival was analysed by Kaplan-Meier curves and Cox regression and was corrected for baseline, procedural, and medical parameters. Self-reported adherence to RASI therapy 3 months after hospital discharge was 94%. Three-year all-cause mortality rates were 12.3% and 20.2% for patients with or without RASI, respectively (log-rank <0.001). In the matched study populations, mortality rates were 14.2% vs. 20.0% (log-rank <0.03). RASI was particularly beneficial in patients with ejection fraction <40% [adjusted hazard ratio (HR) and 95% confidence interval 0.50 (0.29-0.87)], EuroScore II ≥4% [HR 0.47 (0.35-0.65)], or low-flow, low-gradient aortic stenosis [HR 0.53 (0.31-0.93)] who were also on beta-blockers and statins. An association between discharge dosage and survival was observed, with HR 0.75 (0.58-0.96) and 0.57 (0.44-0.72) for patients on <50% and ≥50% target dose, respectively. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) reduced mortality rates similarly (13.9% vs. 9.8%, log-rank 0.103). CONCLUSIONS: The beneficial association between RASI after TAVI and improved survival during follow-up is particularly evident in high-risk patients and may be dose dependent. No superiority was noted in the effectiveness of ACEI or ARB.

Comparison of the Cardiovascular Effects of Two Medetomidine Doses Combined with Tiletamine-Zolazepam for the Immobilization of Red Deer Hinds (Cervus elaphus).

Wild animal immobilization often requires high doses of α2-adrenoceptor agonists. Despite their desired sedative and analgetic effects, well-recognized cardiovascular side effects, such as hypertension and bradycardia, remain a major concern. We compared the effect of two medetomidine doses on intra-arterial blood pressure and heart rate in 13 captive, female red deer (Cervus elaphus) immobilized during winter. Each animal was randomly assigned to receive either 80 µg/kg (group L) or 100 µg/kg (group H) medetomidine, combined with 3 mg/kg tiletamine-zolazepam administered intramuscularly. Changes in cardiovascular variables over time and differences between the groups were analyzed using linear mixed-effect models. Induction time was faster in group L compared with group H; recovery time did not differ between groups. Initially, the arterial blood pressure was higher in group H compared with group L, but differences between groups diminished during anesthesia. Moreover, the decline in arterial blood pressure in group H was more rapid. Heart rate was significantly lower in group L, but bradycardia was not observed. The higher medetomidine dose did not reduce induction time, and initial hypertension was reduced by administering the lower dose. Therefore, although the sample size was small and, thus, the significance of results might be limited, we suggest using 80 µg/kg instead of 100 µg/kg medetomidine when combined with 3 mg/kg tiletamine-zolazepam for the immobilization of female red deer.

Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis.

PURPOSE: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.

Assessment of Benchmark Dose in BEAS-2B Cells by Evaluating the Cell Relative Viability with Particulates in Motorcycle Exhaust via the Air-liquid Interface Exposure.

OBJECTIVE: This study aimed to use an air-liquid interface (ALI) exposure system to simulate the inhalation exposure of motorcycle exhaust particulates (MEPs) and then investigate the benchmark dose (BMD) of MEPs by evaluating cell relative viability (CRV) in lung epithelial BEAS-2B cells. METHODS: The MEPs dose was characterized by measuring the number concentration (NC), surface area concentration (SAC), and mass concentration (MC). BEAS-2B cells were exposed to MEPs at different concentrations via ALI and CRV was determined using Cell Counting Kit (CCK-8) assay. BMD software was applied to calculate BMD and the lower limit of benchmark dose (BMDL) according to Akaike Information Coefficient (AIC), with P-value based on Hill, Linear, Polynomial, and Power model. RESULTS: Our results reveal that BMD of NC and SAC were estimated by the best-fitting Hill model, while MC was estimated by Polynomial model. The BMDL for CRV following ALI exposure to MEPs were as follows: 364.2#/cm 3 for NC; 0.662 × 10 7 nm 2/cm 3 for SAC; and 0.278 µg/m 3 for MC. CONCLUSION: These results indicate that MEPs exposure via ALI system induces a dose-dependent decrease of CRV and provides the potential exposure threshold of MEPs in a lung cell model.

The Intron Retention Variant CsClpP3m Is Involved in Leaf Chlorosis in Some Tea Cultivars.

Tea products made from chlorotic or albino leaves are very popular for their unique flavor. Probing into the molecular mechanisms underlying the chlorotic leaf phenotype is required to better understand the formation of these tea cultivars and aid in future practical breeding. In this study, transcriptional alterations of multiple subunit genes of the caseinolytic protease complex (Clp) in the chlorotic tea cultivar 'Yu-Jin-Xiang' (YJX) were found. Cultivar YJX possessed the intron retention variant of ClpP3, named as CsClpP3m, in addition to the non-mutated ClpP3. The mutated variant results in a truncated protein containing only 166 amino acid residues and lacks the catalytic triad S182-H206-D255. Quantitative analysis of two CsClpP3 variants in different leaves with varying degrees of chlorosis in YJX and analyses of different chlorotic tea cultivars revealed that the transcript ratios of CsClpP3m over CsClpP3 were negatively correlated with leaf chlorophyll contents. The chlorotic young leaf phenotype was also generated in the transgenic tobacco by suppressing ClpP3 using the RNAi method; complementation with non-mutated CsClpP3 rescued the wild-type phenotype, whereas CsClpP3m failed to complement. Taken together, CsClpP3m is involved in leaf chlorosis in YJX and some other tea cultivars in a dose-dependent manner, likely resulting from the failure of Clp complex assembly due to the truncated sequence of CsClpP3m. Our data shed light on the mechanisms controlling leaf chlorosis in tea plants.

The 12-month prevalence of psychotic experiences and their association with clinical outcomes in Hong Kong: an epidemiological and a 2-year follow up studies.

BACKGROUND: The relationship between the subtypes of psychotic experiences (PEs) and common mental health symptoms remains unclear. The current study aims to establish the 12-month prevalence of PEs in a representative sample of community-dwelling Chinese population in Hong Kong and explore the relationship of types of PEs and common mental health symptoms. METHOD: This is a population-based two-phase household survey of Chinese population in Hong Kong aged 16-75 (N = 5719) conducted between 2010 and 2013 and a 2-year follow-up study of PEs positive subjects (N = 152). PEs were measured with Psychosis Screening Questionnaire (PSQ) and subjects who endorsed any item on the PSQ without a clinical diagnosis of psychotic disorder were considered as PE-positive. Types of PEs were characterized using a number of PEs (single v. multiple) and latent class analysis. All PE-positive subjects were assessed with common mental health symptoms and suicidal ideations at baseline and 2-year follow-up. PE status was also assessed at 2-year follow-up. RESULTS: The 12-month prevalence of PEs in Hong Kong was 2.7% with 21.1% had multiple PEs. Three latent classes of PEs were identified: hallucination, paranoia and mixed. Multiple PEs and hallucination latent class of PEs were associated with higher levels of common mental health symptoms. PE persistent rate at 2-year follow-up was 15.1%. Multiple PEs was associated with poorer mental health at 2-year follow-up. CONCLUSIONS: Results highlighted the transient and heterogeneous nature of PEs, and that multiple PEs and hallucination subtype of PEs may be specific indices of poorer common mental health.

Low-dose salinomycin inhibits breast cancer metastasis by repolarizing tumor hijacked macrophages toward the M1 phenotype.

Macrophages are sentinels of the immune system, which are often hijacked by tumor cells to assist tumor growth and metastasis. Herein our results showed that low dose salinomycin (SAL) in the range of 10-50 nM could efficiently induce M1 macrophage polarization in a dose- and time- dependent manner in vitro, with 30 nM SAL being optimal to generate M1-type macrophages from RAW246.7 cells. In animal study, intratumorally injected SAL (50 µg/kg) increased proportion of CD86 cells (by 28.9%), and decreased CD206 cells (by 14.2%) in transplant 4T1 tumors, in comparison with PBS group. Thus it resulted in significant regression in tumor growth (20% tumor inhibition) and pulmonary metastasis (reduced the number of metastatic nodes by 58%) in SAL group, whereas lipopolysaccharide (LPS) and paclitaxel (PTX) groups showed comparable number of metastatic lesions and volume of tumor. LPS treatment could as well lead to inflammatory reactions in tumor with SAL group, but resulted in systemic inflammation (elevated levels of IL-1α, IL-1ß and TNF-α in serum), and PTX (10 µg/kg) treatment increased both types of macrophages. For the first time, we employed salinomycin below the dose of direct antitumor activity could effectively prime M1 type macrophage stimulation and regress tumor growth and metastasis.

Can Statin Treatment Reduce the Risk of Hepatocellular Carcinoma? A Systematic Review and Meta-Analysis.

BACKGROUND: Whether statins can reduce the incidence of cancers has been an interesting topic in recent years. This meta-analysis aimed to determine the relationship between statin treatment with the risk of hepatocellular carcinoma. METHODS: Studies published up to July 2019 were screened from databases. The data from approved studies were pooled. Random-effects or fixed-effects model was used to calculate the relative risk with 95% CIs in the overall group and subgroups. Sensitivity and meta-regression analyses were performed, and publication bias was evaluated. RESULTS: A total of 18 studies involving 1 611 596 patients were included in this meta-analysis. The overall result showed a significantly reduced risk of hepatocellular carcinoma (relative risk = 0.54, 95% CI: 0.42-0.66) in statin users. In comparison to the risk in nonstatin users, the risk of hepatocellular carcinoma was reduced in all subgroups. The dose of statins and their pharmacokinetics can partly explain the heterogeneity in the overall meta-analysis (I2 = 94.6%, P = .000). A dose-dependent effect of statin use for the reduced risk of hepatocellular carcinoma was found. CONCLUSIONS: Findings from this meta-analysis support that statin use can significantly reduce the incidence of hepatocellular carcinoma.

Mulberry branch bark powder significantly improves hyperglycemia and regulates insulin secretion in type II diabetic mice.

This experiment, based on the previous study on R. mori, introduces whole mulberry branch powder into the diet to treat diabetic mice. Mulberry branch bark powder (MBBP) was administered orally to streptozotocin (STZ)-induced type II diabetic (T2D) mice to investigate hypoglycemic effects. After a 4-week period of diet consumption containing 5%, 10% and 20% MBBP, the fasting blood glucose, body weight and the related western blotting were measured, pathologic and immunohistochemical were observed. The 20% MBBP group showed a significant reduction in hyperglycemia and hyperinsulinemia; fasting blood glucose and insulin decreased from 25.0 to 14.8 mmol/L and 26.5 to 16.0 mU/L, respectively. Pathologic and immunohistochemical observation showed that MBBP administration lead to the repair of pancreas cells and restoration of insulin secretion. Dietary MBBP was associated with the decrease in the contents of 3, 4-methylenedioxeamphetamine, 8-OHdG, aspartate aminotransferase, and alanine aminotransferase, and the increase in antioxidative ability and glucose tolerance. Western blotting (WB) analysis suggested that MBBP decreased the TNF-α levels, thus relieving inflammation and improving liver function. It also led to the downregulation of apoptosis factor expression. WB also confirmed that MBBP enhanced the gene expression of the key enzymes: insulin receptor, insulin receptor substrate, p-AKT, GSK3ß, glycogen synthase, G6Pase and phosphoenolpyruvate carboxykinase, which are related to glucose metabolism in the liver, and increase the expression of the genes PDX-1, GLUT2, MafA, and glucokinase, related to insulin secretion. Thus, oral administration of MBBP regulated insulin secretion and effectively maintained normal levels of glucose metabolism in mice, which may be done by improving the antioxidant capacity and activating insulin signaling with T2D..