The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Brain glycogen: A key to revealing the pathology of mental diseases.

Brain glycogen, which is distinct from muscle glycogen and liver glycogen, has become a crucial node linking metabolism, epigenetics, and autophagy. Recent studies have suggested that brain glycogen governs multiple neurobehavioral processes, such as memory formation and consolidation. However, the changes in brain glycogen levels in mental diseases and the associations of these changes with the disease prognosis are unknown. Here, we review the psychological functions of brain glycogen and the different characteristics of astrocytic glycogen and neuronal glycogen. In addition, we summarize the alterations in brain glycogen levels in depression, schizophrenia and sleep disorders, highlighting that brain glycogen functions as an important metabolite responsible for the development of mental diseases. In summary, brain glycogen is a key to understanding the pathology of mental diseases and deserves more attention in future research.

Interfacial engineering of Pickering emulsions stabilized by pea protein-alginate microgels for encapsulation of hydrophobic bioactives.

This study aims to investigate the effects of interfacial layer composition and structure on the formation, physicochemical properties and stability of Pickering emulsions. Interfacial layers were formed using pea protein isolate (PPI), PPI microgel particles (PPIMP), a mixture of PPIMP and sodium alginate (PPIMP-SA), or PPIMP-SA conjugate. The encapsulation and protective effects on different hydrophobic bioactives were then evaluated within these Pickering emulsions. The results demonstrated that the PPIMP-SA conjugate formed thick and robust interfacial layers around the oil droplet surfaces, which increased the resistance of the emulsion to coalescence, creaming, and environmental stresses, including heating, light exposure, and freezing-thawing cycle. Additionally, the emulsion stabilized by the PPIMP-SA conjugate significantly improved the photothermal stability of hydrophobic bioactives, retaining a higher percentage of their original content compared to those in non-encapsulated forms. Overall, the novel protein microgels and the conjugate developed in this study have great potential for improving the physicochemical stability of emulsified foods.

Effectiveness of probiotic- and fish oil-loaded water-in-oil-in-water (W1/O/W2) emulsions at alleviating ulcerative colitis.

Ulcerative colitis (UC) is a common chronic inflammatory disease that causes serious harm to human health. Probiotics have the effect of improving UC. This study evaluated the preventative potential of water-in-oil-in-water (W1/O/W2) emulsions containing both probiotics and fish oil on UC and associated anxiety-like behavior using a mice model. UC model was established in mice by administering dextran sulfate sodium salt (DSS). Free probiotics, probiotic-loaded emulsions, or fish oil and probiotic co-loaded emulsions were then orally administered to the mice. Various bioassays, histological studies, 16s rDNA gene sequencing, and behavioral experiments were conducted to assess changes in the intestinal environment, microbiota, and anxiety-like behavior of the mice. The fish oil and probiotic co-loaded emulsions significantly reduced the inflammatory response by enhancing tight junction protein secretion (ZO-1, Occludin, and Claudin-1), inhibiting pro-inflammatory factors (TNF-α, and IL-1ß), and promoting short-chain fatty acids (SCFAs) production. These emulsions also modified the gut microbiota by promoting beneficial bacteria and suppressing pathogenic bacteria, thereby restoring a balanced gut microbiota. Notably, the emulsions containing both probiotics and fish oil also ameliorated anxiety-like behavior in the mice. The co-delivery of probiotics and fish oil using W1/O/W2 emulsions has shown significant promise in relieving UC and its associated anxiety-like behavior. These findings provide novel insights into the development of advanced therapeutic strategies for treating UC.

Associations of serum glucocorticoid levels on hypertension and blood pressure-related indicators: a nested case-control study in rural China.

BACKGROUND: The relationship between glucocorticoids and hypertension has shown inconsistent findings in previous studies. To address this, our study employed a nested case-control design in rural areas to further investigate the association between serum glucocorticoid levels and hypertension, and blood pressure-related indicators. METHODS: This study employed a nested case-control design, involving 560 pairs of hypertensive cases and matched controls. The concentrations of serum cortisol (F), cortisone (E) and 11-deoxycortisol (S) were determined using liquid chromatography-tandem mass spectrometry. We employed various methods, including generalized linear model (GLM), conditional logistic regression model, restricted cubic spline regression, subgroup analysis, interaction, and joint effects, with adjustments for multiple covariates to analyze the relationships between glucocorticoids, hypertension, and blood pressure-related indicators. RESULTS: After multivariable adjustments, ln-F, ln-F/E, and ln-S were positively associated with SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP), while ln-E was negatively associated with DBP and MAP ( P  < 0.05). Interestingly, ln-S showed no statistically significant association with hypertension prevalence ( P  > 0.05), whereas ln-F and ln-F/E were positively associated with it ( P  < 0.05). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.153 (1.011-1.315) for ln-F and 2.072 (1.622-2.645) for ln-F/E, respectively. In contrast, ln-E exhibited a negative association with hypertension prevalence (adjusted OR = 0.837, 95% CI 0.714-0.982). Moreover, a significant association was observed between the combined use of high-dose F/E and high-dose S with hypertension prevalence (adjusted OR = 3.273, 95% CI 2.013-5.321). Blood pressure indicators and hypertension prevalence significantly increased with elevated serum F and F/E concentrations ( P  < 0.05). Interaction analysis further revealed that among women, the positive association between F/E and hypertension prevalence was more pronounced than in men ( P  < 0.05), and S exhibited a more significant positive association with hypertension prevalence in the overweight population ( P  < 0.05). CONCLUSION: Serum F/E and S levels demonstrated positive associations with hypertension and blood pressure-related indicators, and their combined influence exhibited a synergistic effect on hypertension. Notably, F, F/E, and S were associated with heightened hypertension risk, warranting particular attention in women and overweight populations.

High internal phase double emulsions stabilized by modified pea protein-alginate complexes: Application for co-encapsulation of riboflavin and ß-carotene.

The application of many hydrophilic and hydrophobic nutraceuticals is limited by their poor solubility, chemical stability, and/or bioaccessibility. In this study, a novel Pickering high internal phase double emulsion co-stabilized by modified pea protein isolate (PPI) and sodium alginate (SA) was developed for the co-encapsulation of model hydrophilic (riboflavin) and hydrophobic (ß-carotene) nutraceuticals. Initially, the effect of emulsifier type in the external water phase on emulsion formation and stability was examined, including commercial PPI (C-PPI), C-PPI-SA complex, homogenized and ultrasonicated PPI (HU-PPI), and HU-PPI-SA complex. The encapsulation and protective effects of these double emulsions on hydrophilic riboflavin and hydrophobic ß-carotene were then evaluated. The results demonstrated that the thermal and storage stabilities of the double emulsion formulated from HU-PPI-SA were high, which was attributed to the formation of a thick biopolymer coating around the oil droplets, as well as thickening of the aqueous phase. Encapsulation significantly improved the photostability of the two nutraceuticals. The double emulsion formulated from HU-PPI-SA significantly improved the in vitro bioaccessibility of ß-carotene, which was mainly attributed to inhibition of its chemical degradation under simulated acidic gastric conditions. The novel delivery system may therefore be used for the development of functional foods containing multiple nutraceuticals.

Modulating peppermint oil flavor release properties of emulsion-filled protein gels: Impact of cross-linking method and matrix composition.

For some food applications, it is desirable to control the flavor release profiles of volatile flavor compounds. In this study, the effects of crosslinking method and protein composition on the flavor release properties of emulsion-filled protein hydrogels were explored, using peppermint essential oil as a model volatile compound. Emulsion-filled protein gels with different properties were prepared using different crosslinking methods and gelatin concentrations. Flavor release from the emulsion gels was then monitored using an electronic nose, gas chromatography-mass spectrometry (GC-MS), and sensory evaluation. Enzyme-crosslinked gels had greater hardness and storage modulus than heat-crosslinked ones. The hardness and storage modulus of the gels increased with increasing gelatin concentration. For similar gel compositions, flavor release and sensory perception were faster from the heat-crosslinked gels than the enzyme-crosslinked ones. For the same crosslinking method, flavor release and perception decreased with increasing gelatin concentration, which was attributed to retardation of flavor diffusion through the hydrogel matrix. Overall, this study shows that the release of hydrophobic aromatic substances can be modulated by controlling the composition and crosslinking of protein hydrogels, which may be useful for certain food applications.

New findings on the risk of hypertension from organophosphorus exposure under different glycemic statuses: The key role of lipids?

BACKGROUND AND OBJECTIVE: Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations. METHODS: We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship. RESULTS: The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations. CONCLUSIONS: Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention.

Inflammatory markers and androstenedione modify the effect of serum testosterone on obesity among men: Findings from a Chinese population.

BACKGROUND: Few studies are available on the relationship of androstenedione with inflammation and obesity and the effect of androstenedione and inflammation on the association between testosterone and obesity. This study intended to examine the mediation effect of inflammatory markers on the association of testosterone with obesity and the moderation effect of androstenedione on the association of testosterone with inflammation and obesity in Chinese rural men. MATERIALS AND METHODS: This cross-sectional research enrolled 2536 male rural inhabitants from the Henan Rural Cohort study. The serum concentrations of testosterone and androstenedione were determined by liquid chromatography-tandem mass spectrometry. Linear and logistic regression were used to examine the relationships between testosterone, inflammatory markers, and obesity. Mediation and moderation analyses were carried out to evaluate the potential effects of inflammatory markers on the relationship between testosterone and obesity, as well as androstenedione on the relationships of testosterone with inflammation and obesity. RESULTS: After adjusting for confounding factors, the results showed that testosterone and androstenedione were negatively related to obesity, and inflammatory markers were positively associated with obesity. Besides, testosterone and androstenedione were negatively associated with inflammatory markers. Mediation analysis showed that white blood cell, neutrophil, monocyte, and high-sensitivity C-reactive protein had mediating effects on the association between testosterone and obesity. The most vital mediator was high-sensitivity C-reactive protein, and its proportion of the effect was 11.02% (defined by waist circumference), 11.15% (defined by waist-to-hip ratio), 12.92% (defined by waist-to-height ratio), and full mediating effect (defined by body mass index). Moreover, androstenedione played negative moderation effects on the associations of testosterone with inflammation and obesity. CONCLUSION: Inflammatory markers and androstenedione were first found to have modifying effects on the association of testosterone with obesity. Higher levels of testosterone and androstenedione could reduce the inflammation level and risk of obesity, indicating their potential roles in the prevention and treatment of chronic diseases.

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones.

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes.

Exploring risk factors for totally implantable venous access devices (TIVADs)-related thrombotic occlusion in the off-treatment period.

Totally implantable venous access devices (TIVADs) have been widely used for many years in the management of patients suffering from cancer. Thrombotic occlusion is the most common functional complication in the off-treatment period. This study aims to investigate the incidence of and risk factors for TIVADs-related thrombotic occlusion in patients with breast cancer. The clinical data of 1586 eligible patients with breast cancer with TIVADs at the Fourth Affiliated Hospital of Hebei Medical University from 1 January 2019 to 31 August 2021 were analysed. Thrombotic occlusion was confirmed by angiography with signs of partial or total occlusion. Thrombotic occlusion occurred in 96 (6.1%) cases. Multivariable logistic regression analysis showed that the insertion site of the catheter (P = 0.004), size of the catheter (P < 0.001), and indwelling time (P < 0.001) were significant factors for thrombotic occlusion. Insertion in the right internal jugular vein, smaller catheter size and shorter indwelling time can lower the incidence of thrombotic occlusion in breast cancer patients with TIVADs in the off-treatment period.

Health risks of neonicotinoids chronic exposure and its association with glucose metabolism: A case-control study in rural China.

Since neonicotinoids (NNIs) are widely used around the world, they are extensively distributed in the environment and frequently occurred in humans. This study was conducted to assess the risk of NNIs residues in vegetables and fruits in Henan province, and evaluate the associations of NNIs single and mixed exposure with glucose metabolism, and further explore whether testosterone mediated these relationships in Henan rural population. The data of vegetables and fruits were collected from Henan Province in 2020-2021, and participants were drawn from the Henan Rural Cohort study. Hazard quotient (HQ) and hazard index (HI) were used to assess the risk of exposure to the individual and combined NNIs through vegetables or fruits intake. Relative potency factor (RPF) method was utilized to normalize each NNIs to imidacloprid (IMIRPF). Generalized linear models were used to explore the effects of each NNIs and IMIRPF on glucose metabolism. Weight quartile sum (WQS) regression and Bayesian kernel machine regression (BKMR) model were applied to estimate the effect of NNIs mixtures on glucose metabolism. Mediation analysis was employed to explore whether testosterone mediated these relationships. The HQs and HI in both vegetables and fruits were much lower than 1, which indicated that NNIs in vegetables and fruits were not expected to cause significant adverse effects. However, plasma natural logarithm nitenpyram (Ln_NIT), Ln_thiacloprid-amid (Ln_THD-A), and Ln_IMIeq were positively associated with type 2 diabetes mellitus (T2DM) (odds ratio (OR) (95% confidence interval (CI)): 1.12 (1.05, 1.19), 1.21 (1.10, 1.32), and 1.48 (1.22, 1.80)). Both WQS regression and BKMR models observed significantly positive associations between NNIs mixture exposure and T2DM. Testosterone partially mediated these associations among women (PE = 6.67%). These findings suggest that human NNIs exposure may impair glucose metabolism and could contribute to rising rates of T2DM, and it's necessary to regulate the use of pesticides in rural areas.

Preparation of enzymatically cross-linked α-lactalbumin nanoparticles and their application for encapsulating lycopene.

High internal phase Pickering emulsions (HIPPEs) stabilized by protein nanoparticles have been widely reported, but the use of enzymatic methods for preparing these nanoparticles remains underexplored. Our hypothesis is that enzymatically crosslinked α-lactalbumin (ALA) nanoparticles (ALATGs) prepared using transglutaminase will demonstrate improved properties as stabilizers for HIPPEs. In this study, we investigated the physicochemical properties and microstructures of ALATGs, finding that enzymatic crosslinking could be enhanced by removing Ca2+ ions from ALA and preheating the proteins (85 °C, 15 min). The electrical charge, secondary structure, and surface hydrophobicity of ALATGs were found to depend on crosslinking conditions. HIPPEs formed with an ALA concentration of 10 mg/mL and an enzyme activity of 120 U/g exhibited the highest apparent viscosity and mechanical strength, as well as significantly improved loading capacity and photostability for the encapsulated lycopene. Overall, our results support the hypothesis that ALATG-nanoparticles show superior performance as emulsifiers compared to ALA-nanoparticles.

Pesticide residues in common fruits and vegetables in Henan Province, China.

In this study 3307 samples of 24 vegetables and fruits from 18 regions of Henan Province, China, were collected in 2021 with the aim of assessing the levels of pesticide residues and analysing the differences between different sources in Henan Province. Thirteen kinds of pesticides were analysed by gas chromatography-mass spectrometry (GC-MS) and detection rates were compared by the chi-square test. In all samples, except ginger, pimento, edible fungi and yam, pesticide residues were detected. The detection rates of difenoconazole, acetamiprid, carbendazim, procymidone, emamectin benzoate, lambda-cyhalothrin, cypermethrin and dimethomorph in supermarkets and traditional farmers' markets were different. The difenoconazole group and the dimethomorph group were both statistically different (P < 0.05). This study showed common vegetables and fruits to contain pesticide residues in Henan Province and provided a scientific basis for their evaluation. Different sources take different regulatory measures to control pesticide residues to ensure food safety.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. RESULTS: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. CONCLUSIONS: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure.

An X-ray inactivated vaccine against Pseudomonas aeruginosa Keratitis in mice.

Pseudomonas aeruginosa (P. aeruginosa) is one of the most prevalent pathogens of bacterial keratitis. Bacterial keratitis is a major cause of blindness worldwide. The rising incidence of multidrug resistance of P. aeruginosa precludes treatment with conventional antibiotics. Herein, we evaluated the protective efficiency and explored the possible underlying mechanism of an X-ray inactivated vaccine (XPa) using a murine P. aeruginosa keratitis model. Mice immunized with XPa exhibit reduced corneal bacterial loads and pathology scores. XPa vaccination induced corneal macrophage polarization toward M2, averting an excessive inflammatory reaction. Furthermore, histological observations indicated that XPa vaccination suppressed corneal fibroblast activation and prevented irreversible visual impairment. The potency of XPa against keratitis highlights its potential utility as an effective and promising vaccine candidate for P. aeruginosa.

Co-exposure of organophosphorus pesticides is associated with increased risk of type 2 diabetes mellitus in a Chinese population.

OBJECTIVE: The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure. METHODS: Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (ORs) or ß with 95% confidence intervals (CIs), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM. RESULTS: High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM. CONCLUSION: Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM.

Iruplinalkib (WX­0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer.

Despite remarkable initial responses of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC) patients, cancers eventually develop resistance within one to two years. This study aimed to compare the properties of iruplinalkib (WX­0593) with other ALK inhibitors and report the comprehensive characterization of iruplinalkib against the crizotinib resistance. The inhibitory effect of iruplinalkib on kinase activity was detected. A kinase screen was performed to evaluate the selectivity of iruplinalkib. The effect of iruplinalkib on related signal transduction pathways of ALK and c-ros oncogene 1 (ROS1) kinases was examined. The cellular and in vivo activities of ALK inhibitors were compared in engineered cancer-derived cell lines and in mice xenograft models, respectively. Human hepatocytes derived from three donors were used for evaluating hepatic enzyme inducing activity. HEK293 cell lines expressing transportors were used to invesigated the drug interaction potential mediated by several transporters. The results showed iruplinalkib potently inhibited the tyrosine autophosphorylation of wild-type ALK, ALKL1196M, ALKC1156Y and epidermal growth factor receptor (EGFR)L858R/T790M. The inhibitory effects of iruplinalkib in patient-derived xenograft and cell line-derived xenograft models were observed. Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.

Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.

Exploring differences in symptomatic adverse events assessment between nurses and physicians in the clinical trial setting.

A cross-sectional study was performed at Hebei Medical University Fourth Affiliated Hospital from April to July 2020 to explore the difference and consistency between nurses and physicians in terms of symptomatic adverse event (AE) assessment. The Common Terminology Criteria for Adverse Events (CTCAE) was utilized by nurses and physicians to assess patients' symptomatic AEs. Patients self-reported their AEs utilizing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Four nurses and three physicians were enrolled to assess patients' symptomatic AEs. Given the same AEs, nurses tended to detect more AEs than physicians, and the differences were statistically significant (P < 0.001). The toxicity grade reported by nurses and physicians showed no difference for all AEs, except for fatigue (χ2 = 5.083, P = 0.024). The agreement between nurses and patients was highest compared to the agreement between nurses versus physicians and physicians versus patients. The differences in symptomatic AE assessment can lead to different symptom management. Thus, it is important to establish a collaborative approach between nurses and physicians to ensure continuity in care delivery.