Human dermal exposure to short- and medium-chain chlorinated paraffins: Effect of populations, activities, gender, and haze pollution.

Human dermal exposure to chlorinated paraffins (CPs) has not been well documented. Therefore, hand wipes were collected from four occupational populations to analyze short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) in order to estimate dermal uptake and oral ingestion via hand-to-mouth contact. The total CP levels (∑SCCPs and ∑MCCPs) in wipes ranged from 71.4 to 2310 µg/m2 in security guards, 37.6 to 333 µg/m2 in taxi drivers, 20.8 to 559 µg/m2 in office workers, and 20.9 to 932 µg/m2 in undergraduates, respectively. Security guards exhibited the highest levels of ∑SCCPs among four populations (p < 0.01). In undergraduates engaged in outdoor activities, C13 emerged as the most dominant SCCPs homologue group, followed by C12, C11, and C10. The levels of ∑SCCPs and ∑MCCPs in males in light haze pollution were significantly higher than that in heavy haze pollution (p < 0.05). The median estimated dermal absorption dose of SCCPs and MCCPs via hand was 22.2 and 104 ng (kg of bw)-1 day-1, respectively, approximately 1.5 times the oral ingestion [12.3 and 74.4 ng (kg of bw)-1 day-1], suggesting that hand contact is a significant exposure source to humans.

Sesame lignans modulate aroma formation in sesame oil through the Maillard reaction and lipid oxidation in model systems.

The unknown effect of sesame lignans on aroma formation in sesame oil via the Maillard reaction (MR) and lipid oxidation was investigated. Sesamin, sesamolin, or sesamol was added to 3 models: lysine+glucose (MR), cold-pressed sesame oil (SO), and MR + SO, and were heated at 120 °C for 60 min. All three lignans suppressed SO oxidation while increasing DPPH scavenging ability (p < 0.05). Lignans increased depletions of lysine and glucose and MR browning (p < 0.05). Lignans reduced most aroma-active pyrazines, aldehydes, ketones, alcohols, and esters (p < 0.05). Sesamol and sesamolin increased perceptions of the preferable aromas of nutty, roasted sesame, and popcorn while reducing the undesirable green and rancid aromas (p < 0.05). Sesamol demonstrated a stronger effect on lipid oxidation, MR browning, aroma formation, and sensory perception than sesamin and sesamolin. This study suggests that sesame lignans can modulate aroma formation and sensory perception of sesame oil by interacting with the MR and lipid oxidation pathways.

The interaction between lipid oxidation and the Maillard reaction model of lysine-glucose on aroma formation in fragrant sesame oil.

The formation mechanism behind the sophisticated aromas of sesame oil (SO) has not been elucidated. The interaction effects of the Maillard reaction (MR) and lipid oxidation on the aroma formation of fragrant sesame oil were investigated in model reaction systems made of l-lysine (Lys) and d-glucose (Glc) with or without fresh SO (FSO) or oxidized SO (OSO). The addition of OSO to the Lys-Glc model increased the MR browning at 294 nm and 420 nm and enhanced the DPPH radical scavenging activity greater than the addition of FSO (p < 0.05). The presence of lysine and glucose inhibited the oxidation of sesame oil, reduced the loss of γ-tocopherol, and facilitated the formation of sesamol (p < 0.05). The Maillard-lipid interaction led to the increased concentrations of some of the alkylpyrazines, alkylfurans, and MR-derived ketones and acids (p < 0.05) while reducing the concentrations of other pyrazines, lipid-derived furans, aliphatic aldehydes, ketones, alcohols, and acids (p < 0.05). The addition of FSO to the MR model enhanced the characteristic roasted, nutty, sweet, and fatty aromas in sesame oil (p < 0.05), while excessive lipid oxidation (OSO) brought about an unpleasant oxidized odor and reduced the characteristic aromas. This study helps to understand the sophisticated aroma formation mechanism in sesame oil and provides scientific instruction for precise flavor control in the production of sesame oil.

Can antitrust policy promote enterprise innovation? Evidence from Zhongguancun science and Technology Park.

Emerging countries usually rely on the innovation of enterprises within the regional innovation ecosystem to enhance the national innovation level. However, existing literature lacks insight into how antitrust policies might influence innovation within them. We estimate the impact of the implementation of the Anti-Monopoly Law on enterprise innovation within Zhongguancun Science and Technology Park, China's prominentregional innovation ecosystem. Using a cross-industry difference-in-difference design, we show that greater exposure to competition shock materially boosted enterprise innovation. Antitrust policy promotes enterprise innovation by increasing the R&D investment, human capital, and export. The promotion effect of antitrust is relatively strong in the sample of electronic information industry, firms with low levels of financing constraints, and those that undertake open innovation. Our findings elucidate the nexus between competition and innovation in regional innovation ecosystems and underscore the pivotal role of antitrust policies in the development of Zhongguancun Science and Technology Park.

Understanding the potential of taxi sharing: The case of Chengdu.

The emergence of taxi sharing enhances urban transport efficiency and reduces carbon emissions. Using GPS tracking data from taxis in Chengdu, China, this study first outlines conditions for identifying shareable taxi orders based on their origins and destinations. We then develop a three-phase computational model to optimize matches among all potential shareable orders, calculating the shareable mileage and the proportion of original mileage that could be shared. Our comprehensive temporal and spatial analysis reveal a significant market for taxi sharing in Chengdu, with higher potential on workdays than non-workdays and four distinct demand peaks throughout the day. The morning peak on workdays and the night peak on non-workdays are particularly pronounced. Most shareable orders originate within major city districts. We find a positive correlation between the potential of taxi sharing and average traffic speed, and negative correlations with order volume, regional economic development, and population density. Functional zones related to Enterprises, Motorcycle Services, and Transportation Services exhibit significantly higher sharing potential. Compared to traditional taxi operations, taxi sharing significantly reduces total travel mileage. This quantitative analysis offers insights into the potential demand for taxi sharing among urban residents and may help government authorities optimize taxi resources for the sustainable development of urban transport.

Genetic diversity, clinical uses, and phytochemical and pharmacological properties of safflower (Carthamus tinctorius L.): an important medicinal plant.

Safflower (Carthamus tinctorius L.), a member of the Asteraceae family, is widely used in traditional herbal medicine. This review summarized agronomic conditions, genetic diversity, clinical application, and phytochemicals and pharmacological properties of safflower. The genetic diversity of the plant is rich. Abundant in secondary metabolites like flavonoids, phenols, alkaloids, polysaccharides, fatty acids, polyacetylene, and other bioactive components, the medicinal plant is effective for treating cardiovascular diseases, neurodegenerative diseases, and respiratory diseases. Especially, Hydroxysafflor yellow A (HYSA) has a variety of pharmacological effects. In terms of treatment and prevention of some space sickness in space travel, safflower could be a potential therapeutic agent. Further studies are still required to support the development of safflower in medicine. Our review indicates that safflower is an important medicinal plant and research prospects regarding safflower are very broad and worthy of further investigation.

Preparation, characterization and drug release properties of pH sensitive Zingiber officinale polysaccharide hydrogel beads.

The aim of this study was to prepare a drug carrier that could deliver oral insulin to the intestine. A hydrogel beads composed of sodium carboxymethyl cellulose (CMC), Zingiber offtcinale polysaccharide (ZOP) and chitosan (CS) were prepared by ionic gel method as insulin carrier. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and thermogravimetric (TGA) showed that the hydrogel was formed by metal ion coordination between ZOP and CMC and Fe3+, and CS was coated on the surface of the hydrogel ball in the form of non covalent bond. The results showed that the swelling process of hydrogel spheres has significant pH sensitivity. In addition, the hydrogel beads successfully coated insulin, and the drug loading rate (DL) of (ZOP/CMC-Fe3+)@CS could reach 69.43 ± 7.32 mg/g, and the entrapment efficiency (EE) could reach 66.94 ± 7.43 %. In vitro release experiments, the release rate of (CMC/ZOP-Fe3+)@CS in simulated gastric fluid (SGF) for 2 h was <20 %, and the cumulative release rate of insulin after 9 h in simulated intestinal fluid (SIF) reached over 90 %. The results showed that the hydrogel beads prepared in this work could be used as a potential carrier for delivering oral insulin.

Microplastics could alter invasive plant community performance and the dominance of Amaranthus palmeri.

The increase in alien plant invasions poses a major threat to global biodiversity and ecosystem stability. However, the presence of microplastics (MPs) as an environmental stressor could impact the interactions between invasive and native species in an invasive plant community. Nevertheless, the community alterations and underlying mechanisms resulting from these interactions remain unclear. Herein, we systematically investigated the impacts of polyethylene (PE) and polypropylene (PP) on invasive plant communities invaded by Amaranthus palmeri through soil seed bank. The results illustrated that MPs markedly declined community height and biomass, and altered community structure, low-dose MPs could prominently increase community invasion resistance, but reduced community stability. The niche width and niche overlap of A. palmeri and S. viridis declined when exposed to high-dose MPs, but MPs elicited a significant rise in the niche width of S. salsa. PP had the potential to reduce the diversity of invasive plant community. Structural equation model revealed that PP addition could change soil total phosphorus content, thereby leading to a reduction of the community stability. Our study helps to fill the knowledge gap regarding the effects of MPs on invasive plant communities and provide new perspectives for invasive plant management.

Predicting regional carbon price in China based on multi-factor HKELM by combining secondary decomposition and ensemble learning.

Accurately predicting carbon price is crucial for risk avoidance in the carbon financial market. In light of the complex characteristics of the regional carbon price in China, this paper proposes a model to forecast carbon price based on the multi-factor hybrid kernel-based extreme learning machine (HKELM) by combining secondary decomposition and ensemble learning. Variational mode decomposition (VMD) is first used to decompose the carbon price into several modes, and range entropy is then used to reconstruct these modes. The multi-factor HKELM optimized by the sparrow search algorithm is used to forecast the reconstructed subsequences, where the main external factors innovatively selected by maximum information coefficient and historical time-series data on carbon prices are both considered as input variables to the forecasting model. Following this, the improved complete ensemble-based empirical mode decomposition with adaptive noise and range entropy are respectively used to decompose and reconstruct the residual term generated by VMD. Finally, the nonlinear ensemble learning method is introduced to determine the predictions of residual term and final carbon price. In the empirical analysis of Guangzhou market, the root mean square error(RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the model are 0.1716, 0.1218 and 0.0026, respectively. The proposed model outperforms other comparative models in predicting accuracy. The work here extends the research on forecasting theory and methods of predicting the carbon price.

A nomogram based on biparametric magnetic resonance imaging for detection of clinically significant prostate cancer in biopsy-naïve patients.

PURPOSE: This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients. METHOD: This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong's test. RESULTS: In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83-0.93), 0.90 (95% CI 0.85-0.94), and 0.88 (95% CI 0.83-0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P < 0.01). CONCLUSION: All three scorings had favorite diagnostic accuracy. While in conjunction with age and PSAD the prediction power was significantly improved, and the Model 2 that based on Scoring 2 yielded the highest performance.

Observation of the Effects of Extended Comfort Nursing on Cancer-Related Fatigue in Patients with Lung Cancer Undergoing Chemotherapy.

Objective: This study aimed to evaluate the clinical effects of providing extended comfort care to lung cancer patients undergoing chemotherapy and its impact on cancer-related fatigue levels. Methods: Using a retrospective data analysis approach, a total of 88 lung cancer patients receiving chemotherapy at our hospital from March 2021 to March 2022 were selected as research participants. They were divided into an observation group and a control group based on different nursing methods, with 44 patients in each group. The observation group received extended comfort nursing interventions, while the control group received routine nursing care. Patients' comfort levels in both groups were compared, and changes in cancer-related fatigue, self-efficacy, psychological state, coping style, sleep quality, and overall life quality were assessed. Results: Following the nursing interventions, patients in the observation group exhibited better physical, psychological, spiritual, sociocultural, and environmental well-being compared to the control group (P < .05). The observation group also showed lower scores for emotional exhaustion, physical exhaustion, cognitive exhaustion, and overall exhaustion compared to the control group (P < .05). Moreover, patients in the observation group demonstrated higher levels of self-efficacy on the health promotion strategy questionnaire (Supph) (P < .05) and lower scores on the self-rating anxiety and depressive symptoms scales (P < .05) after receiving nursing care. In terms of coping style, patients in the observation group exhibited lower avoidance and yield scores but higher face scores than the control group (P < .05). The observation group also reported higher overall life quality scale item grades (P < .05) and lower Pittsburgh Sleep Quality Index (PSQI) scores (P < .05) compared to the control group. Conclusions: Extended comfort care for lung cancer patients during chemotherapy improves emotional and physical comfort and effectively reduces cancer-related fatigue levels. These findings have significant implications for clinical practice.

Unveiling the novel role of ryegrass rhizospheric metabolites in benzo[a]pyrene biodegradation.

Rhizoremediation is a promising remediation technology for the removal of soil persistent organic pollutants (POPs), especially benzo[a]pyrene (BaP). However, our understanding of the associations among rhizospheric soil metabolites, functional microorganisms, and POPs degradation in different plant growth stages is limited. We combined stable-isotope probing (SIP), high-throughput sequencing, and metabolomics to analyze changes in rhizospheric soil metabolites, functional microbes, and BaP biodegradation in the early growth stages (tillering, jointing) and later stage (booting) of ryegrass. Microbial community structures differed significantly among growth stages. Metabolisms such as benzenoids and carboxylic acids tended to be enriched in the early growth stage, while lipids and organic heterocyclic compounds dominated in the later stage. From SIP, eight BaP-degrading microbes were identified, and most of which such as Ilumatobacter and Singulisphaera were first linked with BaP biodegradation. Notably, the relationship between the differential metabolites and BaP degradation efficiency further suggested that BaP-degrading microbes might metabolize BaP directly to produce benzenoid metabolites (3-hydroxybenzo[a]pyrene), or utilize benzenoids (phyllodulcin) to stimulate the co-metabolism of BaP in early growth stage; some lipids and organic acids, e.g. 1-aminocyclopropane-1-carboxylic acid, might provide nutrients for the degraders to promote BaP metabolism in later stage. Accordingly, we determined that certain rhizospheric metabolites might regulate the rhizospheric microbial communities at different growth stages, and shift the composition and diversity of BaP-degrading bacteria, thereby enhancing in situ BaP degradation. Our study sheds light on POPs rhizoremediation mechanisms in petroleum-contaminated soils.

Effects of nitrogen stress on uptake and translocation of organophosphate esters by watermifoil (Myriophyllum aquaticum L.) in an aquatic ecosystem.

Although organophosphate esters (OPEs) and nitrogen (N) are normally present in aquatic environments, the effects of the plant uptake, accumulation, and translocation of OPEs in different levels of N remain ambiguous. To better understand these processes, watermifoil (Myriophyllum aquaticum L.) as tested plant was chosen to investigate the effects of different N levels on the uptake and translocation of OPEs by plants in matched water-sediment-plant samples. After two months, we found the root-water concentration factors, root-sediment concentration factors, and translocation factors (TFs) were significantly changed with the levels of N (p < 0.05), implying that the presence of N could alter uptake, accumulation, and translocation of OPEs in M. aquaticum, particularly the process of root absorption. Low concentrations of N could remarkably promote the uptake of OPEs by M. aquaticum. However, when the concentrations of N in water were higher than 200 mg/L, the plants' growth and OPE accumulation by M. aquaticum were obviously inhibited with the elevated N contents. Moreover, the enrichment and environmental transport of OPEs in M. aquaticum seemed to be closely associated with physicochemical parameters; the octanol-water partition coefficient had significant relationships with measured organic carbon-normalized sediment-water partition coefficients and TFs in the present study. Additionally, the substituents and structures of OPEs could also affect the accumulation and translocation of OPEs in M. aquaticum, including the chlorination degree and alkyl chain length. This study could improve our understanding of uptake and translocation of OPEs in aquatic plants under different levels of N.

Biochar may alter plant communities when remediating the cadmium-contaminated soil in the saline-alkaline wetland.

It is thought remediating cadmium pollution with biochar can affect plant traits. However, the potential impact of this practice on plant communities is poorly understood. Here, we established natural-germinated plant communities using soil seed bank from a saline-alkaline wetland and applied a biochar treatment in Cd-polluted wetland soil. The outcomes illustrated that Juglans regia biochar (JBC), Spartina alterniflora biochar (SBC), and Flaveria bidentis biochar (FBC) promoted exchangeable Cd transform into FeMn oxide bound Cd. Additionally, most biochar addition reduced species abundance, root-shoot ratio, biomass, diversity, and community stability, yet enhanced community height. Among all treatments, the 5 % SBC demonstrated the most significant reduction in species abundance, biomass, species richness and functional richness. Specifically, it resulted in a reduction of 92.80 % in species abundance, 73.80 % in biomass, 66.67 % in species richness, and 95.14 % in functional richness compared to the CK. We also observed changes in root morphological traits and community structure after biochar addition. Soil pH, salinity, and nutrients played a dominant role in shaping plant community. These findings have implications for biodiversity conservation, and the use of biochar for the remediation of heavy metals like cadmium should be approached with caution due to its potential negative impacts on plant communities.

Research progress on the structural characterization, biological activity and product application of polysaccharides from Crataegus pinnatifida.

Crataegus pinnatifida is a plant of the Crataegus genus in the Rosaceae family and is commonly used as a food and medicinal resource. Crataegus pinnatifida polysaccharide, as one of the main active ingredients of Crataegus pinnatifida, has a variety of beneficial biological activities, such as antioxidant, hypoglycemic activity, lipid-lowering, intestinal flora regulation, promotion immune regulation, and antitumor activities. However, the extraction methods of Crataegus pinnatifida polysaccharides lack innovation, the primary structure is relatively limited, and the biological activity mechanism needs to be further explored. Therefore, this review summarizes the research status of the extraction, purification, structural characterization, biological activity, and product application of Crataegus pinnatifida polysaccharides. The purpose of this study is to generate support for further development and application of polysaccharides from Crataegus pinnatifida.

Effects of Extraction Methods on the Physicochemical Properties and Biological Activities of Polysaccharides from Polygonatum sibiricum.

Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze-thaw-assisted extraction (FAE) were used to extract PSPs, and their structure-activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure-activity relationship of PSPs.

Structural Characterization, Simulated Digestion and Anti-Aging Activities of an Acidic Polysaccharide from Salvia Miltiorrhiza.

An acidic polysaccharide (SMP) with a molecular weight (Mw) of 1.28 × 106 Da was isolated from Salvia miltiorrhiza. The monosaccharide composition in molar percentages was rhamnose (Rha): galacturonic acid (GalA): galactose (Gal): arabinose (Ara) = 6.15: 55.98: 21.27: 16.69. The results of simulated digestion in vitro showed that SMP was not degraded in saliva, gastric juice or intestinal juice. The Y maze test and new object recognition test showed that SMP could improve the working memory impairment of aging mice. SMP could also increase the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and brain tissue, decrease the content of malondialdehyde (MDA), decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue, and increase the content of short-chain fatty acids (SCFA) in the intestine. In addition, SMP could also regulate the intestinal flora structure, including increasing the relative abundance of Firmicutes and Bacteroidetes and decreasing the relative abundance of Proteobacteria. This work lays a foundation for the development of functional foods related to Salvia miltiorrhiza.

Uptake, accumulation, and translocation of organophosphate esters by watermifoil (Myriophyllum aquaticum) in an aquatic ecosystem: effects of chemical structure and concentrations.

In order to explore the environmental behavior of organophosphate esters (OPEs) in aquatic environment, the accumulation and distribution of OPEs in water, sediment, and plant were investigated. In this study, watermifoil (Myriophyllum aquaticum) were exposed with ten OPEs for concentrations of 200 ng/g, 500 ng/g, 1000 ng/g, and 2000 ng/g, respectively. The concentrations of Σ10OPEs in rhizosphere sediment were higher than those in non-rhizosphere sediment, demonstrating that rhizosphere processes tend to transport OPEs into the rhizosphere sediment. Most of the selected OPEs were not in equilibrium between water and sediment, and trend to retain in sediment. In addition, OPEs with relatively higher hydrophobicity had trend to retained in Myriophyllum aquaticum roots, whereas OPEs with lower hydrophobicity were more likely transported to shoots. In this study, octanol-water partition coefficient (KOW) had significantly positive correlations with organic carbon-normalized soil-water partition coefficients (KOC) and root-water concentration factors (RWCFs), but KOW was negatively correlated with translocation factors (TFs). Moreover, the substituent types and initial levels of OPEs also have impacts on the plant uptake and accumulation. These observations will improve our understanding of the distribution and translocation of OPEs in aquatic environment.

Olanzapine/Samidorphan in Young Adults With Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder Who Are Early in Their Illness: Results of the Randomized, Controlled ENLIGHTEN-Early Study.

Objective: Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness.Methods: Young adults (16-39 years) with DSM-5 schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m2, and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d). Primary endpoint was percent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, waist circumference change, and Clinical Global Impressions-Severity (CGI-S) change.Results: Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed. Percent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% vs 6.77%; least-squares mean [LSM] [SE] difference, -1.87% [0.75]; P = .012). Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% vs 30.4%, respectively; OR = 0.64; 95% CI = 0.39 to 1.05); hierarchical testing precluded further statistical evaluation of secondary endpoints. Proportions of patients with ≥ 7% weight gain (33.1% vs 44.8%; OR = 0.61, 95% CI = 0.39 to 0.94) and waist circumference change (2.99 vs 3.90 cm; LSM [SE] difference, -0.92 cm [0.58]; 95% CI = -2.06 to 0.22) favored OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was -0.82 (0.06). OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes.Conclusions: In patients with early-phase schizophrenia, schizophreniform disorder, or BD-I, OLZ/SAM treatment resulted in less weight gain versus olanzapine.Trial Registration: ClinicalTrials.gov identifier: NCT03187769.

Proliferation toxicity and mechanism of novel mixed bromine/chlorine transformation products of tetrabromobisphenol A on human embryonic stem cell.

Mixed bromine/chlorine transformation products of tetrabromobisphenol A (ClyBrxBPAs) are mixed halogenated-type compounds recently identified in electronic waste dismantling sites. There are a lack of toxicity data on these compounds. To study their development toxicity, the proliferation toxicity was investigated using human embryonic stem cells (hESC) exposed to the lowest effective dose of two ClyBrxBPA analogues (2-chloro-2',6-dibromobisphenol A and 2,2'-dichloro-6-monobromobisphenol A). For comparison, tetrabromobisphenol A, 2,2',6-tribromobisphenol A, and bisphenol A were also assessed. It was observed that ClyBrxBPAs inhibited hESCs proliferation in a concentration-dependent manner. The cell bioaccumulation efficiency of ClyBrxBPAs was higher than that of tetrabromobisphenol A. Also, ClyBrxBPAs were more toxic than tetrabromobisphenol A, with 2,2'-dichloro-6-monobromobisphenol A exhibiting the most potent toxicity. Furthermore, flow cytometry and oxidative stress results showed that increased reactive oxygen species raised the degree of apoptosis and reduced DNA synthesis. Metabolomics analysis on the effect of ClyBrxBPAs on metabolic pathway alteration showed that ClyBrxBPAs mainly interfered with four metabolic pathways related to amino acid metabolism and biosynthesis. These results provide an initial perspective on the proliferation toxicity of ClyBrxBPAs, indicating development toxicity in children.