Probing Long-Term Impacts: Low-Dose Polystyrene Nanoplastics Exacerbate Mitochondrial Health and Evoke Secondary Glycolysis via Repeated and Single Dosing.

Nanoplastics (NPs) are omnipresent in the environment and contribute to human exposure. However, little is known regarding the long-term effects of NPs on human health. In this study, human intestinal Caco-2 cells were exposed to polystyrene nanoplastics (nanoPS) in an environmentally relevant concentration range (102-109 particles/mL) under two realistic exposure scenarios. In the first scenario, cells were repeatedly exposed to nanoPS every 2 days for 12 days to study the long-term effects. In the second scenario, only nanoPS was added once and Caco-2 cells were cultured for 12 days to study the duration of the initial effects of NPs. Under repeated dosing, initial subtle effects on mitochondria induced by low concentrations would accrue over consistent exposure to nanoPS and finally lead to significant impairment of mitochondrial respiration, mitochondrial mass, and cell differentiation process at the end of prolonged exposure, accompanied by significantly increased glycolysis over the whole exposure period. Single dosing of nanoPS elicited transient effects on mitochondrial and glycolytic functions, as well as increased reactive oxygen species (ROS) production in the early phase of exposure, but the self-recovery capacity of cells mitigated these effects at intermediate culture times. Notably, secondary effects on glycolysis and ROS production were observed during the late culture period, while the cell differentiation process and mitochondrial mass were not affected at the end. These long-term effects are of crucial importance for comprehensively evaluating the health hazards arising from lifetime exposure to NPs, complementing the extensively observed acute effects associated with prevalent short-term exposure to high concentrations. Our study underlines the need to study the toxicity of NPs in realistic long-term exposure scenarios such as repeated dosing.

Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway.

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

Identification of Poly(ethylene terephthalate) Nanoplastics in Commercially Bottled Drinking Water Using Surface-Enhanced Raman Spectroscopy.

Micro/nanoplastics have emerged as global contaminants of serious concern to human and ecosystem health. However, identification and visualization of microplastics and particularly nanoplastics have remained elusive due to the lack of feasible and reliable analytical approaches, particularly for trace nanoplastics. Here, an efficient surface-enhanced Raman spectroscopy (SERS)-active substrate with triangular cavity arrays is reported. The fabricated substrate exhibited high SERS performance for standard polystyrene (PS) nanoplastic detection with size down to 50 nm and a detection limit of 0.001% (1.5 × 1011 particles/mL). Poly(ethylene terephthalate) (PET) nanoplastics collected from commercially bottled drinking water were detected with an average mean size of ∼88.2 nm. Furthermore, the concentration of the collected sample was estimated to be about 108 particles/mL by nanoparticle tracking analysis (NTA), and the annual nanoplastic consumption of human beings through bottled drinking water was also estimated to be about 1014 particles, assuming water consumption of 2 L/day for adults. The facile and highly sensitive SERS substrate provides more possibilities for detecting trace nanoplastics in an aquatic environment with high sensitivity and reliability.

Effect of various repositioning regimens on pressure wound ulcer occurrence in at-risk adult persons without existing pressure wound ulcers: A meta-analysis.

Meta-analysis research was implemented to appraise the effect of various repositioning regimens (RRs) on pressure wound ulcer (PWU) occurrence in at-risk adult persons without existing PWUs. Inclusive literature research till April 2023 was done and 1197 interconnected researches were revised. The 15 picked researches, enclosed 8510 at-risk adult persons without existing PWUs persons were in the utilised researchers' starting point, 1002 of them were utilising repositioning, 1069 were control, 3443 were utilising 2-<4 h repositioning and 2994 were utilising 4-6 h repositioning. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the consequence of various RRs on PWU occurrence in at-risk adult persons without existing PWUs by the dichotomous approach and a fixed or random model. Repositioning had significantly lower PWU (OR, 0.49; 95% CI, 0.32-0.73, p < 0.001) compared to control in at-risk adult persons without existing PWUs persons. 2-<4 h repositioning had significantly lower PWU (OR, 0.62; 95% CI, 0.42-0.90, p = 0.01) compared to 4-6 h repositioning in at-risk adult persons without existing PWUs persons. Repositioning had significantly lower PWU compared to control in at-risk adult persons without existing PWU persons. 2-<4 h repositioning had significantly lower PWU compared to 4-6 h repositioning in at-risk adult persons without existing PWUs persons. However, caution needs to be taken when interacting with its values since there was a low sample size of some of the chosen research found for the comparisons in the meta-analysis.

Enhanced optical trapping of ZrO2@TiO2 photonic force probe with broadened solvent compatibility.

Optical trapping and manipulating nanoparticles are essential tools for interrogating biomedicine at the limits of space and time. Typically, silica or polystyrene microspheres are used as photonic force probes. However, adapting those probes to organic solvents is an ongoing challenge due to the limited solvent compatibility and low refractive index mismatch. Here we report on the optical force enhancement and solvent compatibility that utilizes ZrO2@TiO2 core-shell nanoparticles. We experimentally demonstrate that the 450-nm-diameter ZrO2@TiO2 core-shell nanoparticles achieve the lateral and axial trap stiffness up to 0.45 pN µm-1 mW-1 and 0.43 pN µm-1 mW-1 in water, showing more than fivefold and ninefold improvement on the ordinary SiO2 particle of the same size. In addition, ZrO2@TiO2 core-shell nanoparticles can realize stable three-dimensional trapping in both polyethylene glycol and glucose solutions. This optical trapping enhancement property, coupled with solvent compatibility, expands the range of feasible optical trapping experiments and will pave the way toward more advanced biological applications.

Manipulation force analysis of nanoparticles with ultra-high numerical aperture metalens.

Metalens optical tweezers technology has several advantages for manipulating micro-nano particles and high integration. Here, we used particle swarm optimization (PSO) to design a novel metalens tweezer, which can get 3-dimensional trapping of particles. The numerical aperture (NA) of the metalens can reach 0.97 and the average focusing efficiency is 44%. Subsequently, we analyzed the optical force characteristics of SiO2 particles with a radius of 350 nm at the focal point of the achromatic metalens. We found the average maximum force of SiO2 particles in the x-direction and z-direction to be 0.88 pN and 0.72 pN, respectively. Compared with the dispersive metalens, it is beneficial in maintaining the constant of optical force, the motion state of trapped particles, and the stability of the trapping position.

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

Transcriptome and metabolome profiling provide insights into molecular mechanism of pseudostem elongation in banana.

BACKGROUND: Banana plant height is an important trait for horticultural practices and semi-dwarf cultivars show better resistance to damages by wind and rain. However, the molecular mechanisms controlling the pseudostem height remain poorly understood. Herein, we studied the molecular changes in the pseudostem of a semi-dwarf banana mutant Aifen No. 1 (Musa spp. Pisang Awak sub-group ABB) as compared to its wild-type dwarf cultivar using a combined transcriptome and metabolome approach. RESULTS: A total of 127 differentially expressed genes and 48 differentially accumulated metabolites were detected between the mutant and its wild type. Metabolites belonging to amino acid and its derivatives, flavonoids, lignans, coumarins, organic acids, and phenolic acids were up-regulated in the mutant. The transcriptome analysis showed the differential regulation of genes related to the gibberellin pathway, auxin transport, cell elongation, and cell wall modification. Based on the regulation of gibberellin and associated pathway-related genes, we discussed the involvement of gibberellins in pseudostem elongation in the mutant banana. Genes and metabolites associated with cell wall were explored and their involvement in cell extension is discussed. CONCLUSIONS: The results suggest that gibberellins and associated pathways are possibly developing the observed semi-dwarf pseudostem phenotype together with cell elongation and cell wall modification. The findings increase the understanding of the mechanisms underlying banana stem height and provide new clues for further dissection of specific gene functions.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial.

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA.

Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic and prognostic biomarkers. Bioinformatics and translation omics have begun to elucidate the roles and modes of action of the functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) and circular RNA (circRNA)-encoded small peptides are compiled and synthesized. We introduce both the computational and analytical methods used to forecast prospective ncRNAs encoding oncologically functional oligopeptides. We also present numerous specific lncRNA and circRNA-encoded proteins and their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite the discovery, development, and optimization of novel and efficacious cancer diagnostic, therapeutic, and prognostic protein-based tools derived from non-coding RNAs. The role of ncRNA-encoding functional peptides has promising application perspectives and potential challenges in cancer research. The aim of this review is to provide a theoretical basis and relevant references, which may promote the discovery of more functional peptides encoded by ncRNAs, and further develop novel anticancer therapeutic targets, as well as diagnostic and prognostic cancer markers.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Relationship between topological efficiency in white matter structural networks with cerebral oxygen metabolism in young adults.

The relationship between the topological characteristics of the white matter (WM) network have been shown to be related to neural development, intelligence, and various diseases; however, few studies have been conducted to explore the relationship between topological characteristics of the WM network and cerebral metabolism. In a recent study we investigated the relationship between WM network topological and metabolic metrics of the cerebral parenchyma in healthy volunteers using the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique and graph theory approaches. Ninety-six healthy adults (25.5 ±â€¯1.8 years of age) were recruited as volunteers in the current study. The cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction, and the global topological metrics of the WM network (global efficiency [Eglob], local efficiency, and small-worldliness) were assessed. A stepwise multiple linear regression model was estimated. CMRO2 was entered as the dependent variable. The topological and demographic parameters (age, gender, FIQ, SBP, gray matter volume, and WM volume) were entered as independent variables in the model. The final performing models were comprised of predictors of Eglob, FIQ, and age (adjusted R2 values were 0.489 [L-AAL] and 0.424 [H-1024]). Our study initially revealed a relationship between Eglob and cerebral oxygen metabolism in healthy young adults.

Neoantigen vaccine: an emerging tumor immunotherapy.

Genetic instability of tumor cells often leads to the occurrence of a large number of mutations, and expression of non-synonymous mutations can produce tumor-specific antigens called neoantigens. Neoantigens are highly immunogenic as they are not expressed in normal tissues. They can activate CD4+ and CD8+ T cells to generate immune response and have the potential to become new targets of tumor immunotherapy. The development of bioinformatics technology has accelerated the identification of neoantigens. The combination of different algorithms to identify and predict the affinity of neoantigens to major histocompatibility complexes (MHCs) or the immunogenicity of neoantigens is mainly based on the whole-exome sequencing technology. Tumor vaccines targeting neoantigens mainly include nucleic acid, dendritic cell (DC)-based, tumor cell, and synthetic long peptide (SLP) vaccines. The combination with immune checkpoint inhibition therapy or radiotherapy and chemotherapy might achieve better therapeutic effects. Currently, several clinical trials have demonstrated the safety and efficacy of these vaccines. Further development of sequencing technologies and bioinformatics algorithms, as well as an improvement in our understanding of the mechanisms underlying tumor development, will expand the application of neoantigen vaccines in the future.

Tumor Extracellular pH-Driven Cancer-Selective Artificial Receptor-Mediated Tumor-Targeted Fluorescence Imaging.

Biomarker receptors on cancer cells can sense and recruit extracellular ligands and ligand-conjugated imaging agents/drugs, providing a critical basis upon which to develop an active tumor-targeting strategy. However, such a strategy can be confounded by both the limited number of cancer biomarker receptors and the inherent heterogeneity of cancer cells. Therefore, we herein report a simple strategy to deploy an exogenous physical label on the surface of cancer cells as an artificial receptor (AR) for active tumor targeting. It can be driven by the tumor extracellular acidic microenvironment to insert into the plasma membrane of cancer cells. Our studies demonstrated that an AR could efficiently sense and recruit the extracellular imaging agent Cy5-streptavidin conjugate to cancer cells, cancer cell spheroids, and an in vivo tumor. Based on the easy synthesis and chemical modification diversity of the peptide, our AR holds promise as a novel tumor-targeted strategy.

Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y Gastric Bypass, RYGB, is the most effective strategy to control body weight in morbid obesity. RYGB leads to rapid improvement of glycemic status and weight loss, which are largely attributed to the alteration of gastrointestinal hormones including ghrelin. The current study examined potential mechanisms of altered ghrelin synthesis after RYGB. METHODS: Gastric mammalian target of rapamycin (mTOR) signaling, ghrelin synthesis and secretion were determined in lean or obese male mice with or without RYGB operation, as well as in obese patients pre- and post-RYGB surgery. Ghrelin expression and mTOR signaling were investigated by western blotting and immunohistochemistry. Ghrelin mRNA levels were detected by real-time PCR. Plasma ghrelin was measured by enzyme immunoassay. RESULTS: mTOR activity in the gastric fundus was significantly lower than in the forestomachs. Both of them were decreased after 24h fasting. A significant negative correlation was found between gastric levels of phospho-S6 (phospho-S6 ribosomal protein) and proghrelin during changes of energy status. mTOR activity was activated, whereas ghrelin expression was inhibited by Roux-en-Y Gastric Bypass in both rodents and human beings. Increment of ghrelin synthesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in both lean and obese mice. Administration of Ad-S6K1 (adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1) from tail vein suppressed the expression of ghrelin in RYGB-operated mice relative to control animals. CONCLUSION: mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of ghrelin after Roux-en-Y Gastric Bypass.

Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep.

A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole-brain cerebral metabolic rate of oxygen (CMRO2 ), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase-contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age- and sex-matched control volunteers (n = 39) during natural sleep to assess whole-brain CMRO2 , CBF, OEF, and arousal from sleep scores. Results showed that whole-brain CMRO2 and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp 38:2532-2539, 2017. © 2017 Wiley Periodicals, Inc.

OLT-centralized sampling frequency offset compensation scheme for OFDM-PON.

We propose an optical line terminal (OLT)-centralized sampling frequency offset (SFO) compensation scheme for adaptively-modulated OFDM-PON systems. By using the proposed SFO scheme, the phase rotation and inter-symbol interference (ISI) caused by SFOs between OLT and multiple optical network units (ONUs) can be centrally compensated in the OLT, which reduces the complexity of ONUs. Firstly, the optimal fast Fourier transform (FFT) size is identified in the intensity-modulated and direct-detection (IMDD) OFDM system in the presence of SFO. Then, the proposed SFO compensation scheme including phase rotation modulation (PRM) and length-adaptive OFDM frame has been experimentally demonstrated in the downlink transmission of an adaptively modulated optical OFDM with the optimal FFT size. The experimental results show that up to ± 300 ppm SFO can be successfully compensated without introducing any receiver performance penalties.

Elevated circulating Neuregulin4 level in patients with diabetes.

BACKGROUND: Neuregulin4 (Nrg4) is a novel adipokine expressed in adipose tissues, enriched in brown adipose tissue, and able to improve whole-body metabolism in rodent, thus having the potential to treat obesity-associated disorders such as diabetes. However, the association between serum Nrg4 levels and diabetes risk in human remains unclear. This study was designed to examine circulating Nrg4 levels in subjects with different glucose tolerance status. METHODS: Age-, sex-, and body mass index-matched subjects (n = 310: 83 normal glucose tolerance [NGT], 129 prediabetes, and 96 diabetes) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal study (Reaction study) were included. Serum Nrg4 was measured via enzyme-linked immunosorbent assay. Basic anthropometric parameters, fasting plasma glucose and 2-hours postload plasma glucose, hemoglobin A1c , and serum lipid profile were also measured. RESULTS: The serum Nrg4 levels were higher in patients with diabetes than those with NGT and prediabetes (diabetes: 396.8[65.9, 709.4], NGT: 80.1[0, 554.1], prediabetes: 168.0[32.9, 463.9] pg/mL [median (interquartile range), both P < 0.05]). The Nrg4 concentration was correlated with fasting plasma glucose. When the top versus bottom quartiles of serum Nrg4 concentrations were compared with adjustment for age and sex, an odds ratio of 3.005 was observed in diabetes prevalence, which persisted after adjusting other potential confounding variables. Other nonglucose parameters as body mass index; waist, hip, and neck circumferences; alanine aminotransferase; triglyceride; high-density lipoprotein; uric acid; and estimated glomerular filtration rate were also correlated with serum Nrg4 (P < 0.05). CONCLUSIONS: The circulating Nrg4 level is elevated in the prediabetic and diabetic patients compared to control and is an independent risk factor associated with diabetes.

Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.

Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC50=0.62 ± 0.04 and 1.92 ± 0.09 µM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO2 will result in a moderate to dramatic decrease in potency.

Vitamin E: An assistant for black soldier fly to reduce cadmium accumulation and toxicity.

Cadmium (Cd) is a toxic heavy metal associated with osteoporosis, liver, and kidney disease. The black soldier fly (BSF) Hermetia illucens may be exposed to Cd during the transformation of livestock manure. The BSF has a high tolerance to Cd. In the previous work of the laboratory, we found that vitamin E (VE) may play a role in the tolerance of BSF to Cd exposure. The main findings are as follows: The BSF larvae pretreated with exogenous VE had heavier body weight, lower content and toxicity of Cd under similar Cd exposure. Even in high Cd exposure at the concentrations of 300 and 700 mg/kg, the BSF larvae pretreated with exogenous VE at a concentration of 100 mg/kg still reduced the Cd toxicity to 85.33 % and 84.43 %, respectively. The best-fitting models showed that metallothionein (MT) content, oxidative damage (8-hydroxydeoxyguanosine content, malondialdehyde content), antioxidant power (total antioxidant power, peroxidase activity) had a great influence on content and toxicity of Cd bioaccumulated in the larvae. The degree of oxidative damage was reduced in the larvae with exogenous VE pretreatments. This variation can be explained by their changed MT content and increased antioxidant power because of exogenous VE. These results reveal the roles of VE in insects defense against Cd exposure and provide a new option for the prevention and therapy of damage caused by Cd exposure.