Development and validation of a prediction model for suboptimal ovarian response in polycystic ovary syndrome (PCOS) patients undergoing GnRH-antagonist protocol in IVF/ICSI cycles.

BACKGROUND: PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients. METHODS: This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model. RESULTS: The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157-0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability. CONCLUSION: The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.

A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors.

Transcriptome-wide association studies (TWAS) have provided valuable insight in identifying genes that may impact cigarette smoking. Most of previous studies, however, mainly focused on European ancestry. Limited TWAS studies have been conducted across multiple ancestries to explore genes that may impact smoking behaviors. In this study, we used cis-eQTL data of cerebral cortex from multiple ancestries in MetaBrain, including European, East Asian, and African samples, as reference panels to perform multi-ancestry TWAS analyses on ancestry-matched GWASs of four smoking behaviors including smoking initiation, smoking cessation, age of smoking initiation, and number of cigarettes per day in GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Multiple-ancestry fine-mapping approach was conducted to identify credible gene sets associated with these four traits. Enrichment and module network analyses were further performed to explore the potential roles of these identified gene sets. A total of 719 unique genes were identified to be associated with at least one of the four smoking traits across ancestries. Among those, 249 genes were further prioritized as putative causal genes in multiple ancestry-based fine-mapping approach. Several well-known smoking-related genes, including PSMA4, IREB2, and CHRNA3, showed high confidence across ancestries. Some novel genes, e.g., TSPAN3 and ANK2, were also identified in the credible sets. The enrichment analysis identified a series of critical pathways related to smoking such as synaptic transmission and glutamate receptor activity. Leveraging the power of the latest multi-ancestry GWAS and eQTL data sources, this study revealed hundreds of genes and relevant biological processes related to smoking behaviors. These findings provide new insights for future functional studies on smoking behaviors.

Predictive modeling of methylmercury in rice (Oryza sativa L.) and species-sensitivity-distribution-based derivation of the threshold of soil mercury in karst mountain areas.

The bioavailable mercury (Hg) in the soil is highly active and can affect the formulation of methyl-Hg (MeHg) in soil and its accumulation in rice. Herein, we predicted the concentration of MeHg in rice using bioavailable Hg extracted from soils; additionally, we determined the threshold value of soil Hg in karst mountain areas based on species sensitivity distribution. The bioavailable Hg was extracted using calcium chloride, hydrochloric acid (HCl), diethylenetriaminepentaacetic acid mixture, ammonium acetate, and thioglycolic acid. Results showed that HCl is the best extractant, and the prediction model demonstrated good predictability of the MeHg concentration in rice based on the HCl-extractable Hg, pH, and soil organic matter (SOM) data. Compared with the actual MeHg concentration in rice, approximately 99% of the predicted values (n = 103) were within the 95% prediction range, indicating the good performance of the rice MeHg prediction model based on soil pH, SOM, and bioavailable Hg in karst mountain areas. Based on this MeHg prediction model, the safety threshold of soil Hg was calculated to be 0.0936 mg/kg, which is much lower than the soil pollution risk screening value of agricultural land (0.5 mg/kg), suggesting that a stricter standard should be applied regarding soil Hg in karst mountain areas. This study presents the threshold of soil Hg pollution for rice safety in karst mountain areas, and future studies should target this threshold range.

Development and validation of a prediction model for unexpected poor ovarian response during IVF/ICSI.

Background: Identifying poor ovarian response (POR) among patients with good ovarian reserve poses a significant challenge within reproductive medicine. Currently, there is a lack of published data on the potential risk factors that could predict the occurrence of unexpected POR. The objective of this study was to develop a predictive model to assess the individual probability of unexpected POR during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments. Methods: The development of the nomogram involved a cohort of 10,404 patients with normal ovarian reserve [age, ≤40 years; antral follicle count (AFC), ≥5; and anti-Müllerian hormone (AMH), ≥1.2 ng/ml] from January 2019 to December 2022. Univariate regression analyses and least absolute shrinkage and selection operator regression analysis were employed to ascertain the characteristics associated with POR. Subsequently, the selected variables were utilized to construct the nomogram. Results: The predictors included in our model were body mass index, basal follicle-stimulating hormone, AMH, AFC, homeostasis model assessment of insulin resistance (HOMA-IR), protocol, and initial dose of gonadotropin. The area under the receiver operating characteristic curve (AUC) was 0.753 [95% confidence interval (CI) = 0.7257-0.7735]. The AUC, along with the Hosmer-Lemeshow test (p = 0.167), demonstrated a satisfactory level of congruence and discrimination ability of the developed model. Conclusion: The nomogram can anticipate the probability of unexpected POR in IVF/ICSI treatment, thereby assisting professionals in making appropriate clinical judgments and in helping patients to effectively manage expectations.

Combining Classic and Novel Neutrophil-Related Biomarkers to Identify Non-Small-Cell Lung Cancer.

BACKGROUND: Recent studies have revealed that neutrophils play a crucial role in cancer progression. This study aimed to explore the diagnostic value of neutrophil-related biomarkers for non-small-cell lung cancer (NSCLC). METHODS: We initially assessed the associations between classic neutrophil-related biomarkers (neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (NEU), absolute lymphocyte counts (LYM)) and NSCLC in 3942 cases and 6791 controls. Then, we measured 11 novel neutrophil-related biomarkers via Luminex Assays in 132 cases and 66 controls, individually matching on sex and age (±5 years), and evaluated their associations with NSCLC risk. We also developed the predictive models by sequentially adding variables of interest and assessed model improvement. RESULTS: Interleukin-6 (IL-6) (odds ratio (OR) = 10.687, 95% confidence interval (CI): 3.875, 29.473) and Interleukin 1 Receptor Antagonist (IL-1RA) (OR = 8.113, 95% CI: 3.182, 20.689) shows strong associations with NSCLC risk after adjusting for body mass index, smoking status, NLR, and carcinoembryonic antigen. Adding the two identified biomarkers to the predictive model significantly elevated the model performance from an area under the receiver operating characteristic curve of 0.716 to 0.851 with a net reclassification improvement of 97.73%. CONCLUSIONS: IL-6 and IL-1RA were recognized as independent risk factors for NSCLC, improving the predictive performance of the model in identifying disease.

The involvement of Neuregulin-1 in the process of facial nerve injury repair through the utilization of dental pulp stem cells.

BACKGROUND: Facial nerve injury often results in poor prognosis due to the challenging process of nerve regeneration. Neuregulin-1, a human calmodulin, is under investigation in this study for its impact on the reparative capabilities of Dental Pulp Stem Cells (DPSCs) in facial nerve injury. METHODS: Lentivirus was used to transfect and construct Neuregulin-1 overexpressed DPSCs. Various techniques assessed the effects of Neuregulin-1: osteogenic induction, lipid induction, Reverse Transcription Polymerase Chain Reaction, Western Blot, Cell Counting Kit-8 assay, wound healing, immunofluorescence, Phalloidin staining, nerve stem action potential, Hematoxylin-eosin staining, transmission electron microscopy, and immunohistochemistry. RESULTS: Neuregulin-1 effectively enhanced the proliferation, migration, and cytoskeletal rearrangement of DPSCs, while simultaneously suppressing the expression of Ras homolog gene family member A (RhoA) and Microfilament actin (F-actin). These changes facilitated the neural differentiation of DPSCs. Additionally, in vivo experiments showed that Neuregulin-1 expedited the restoration of action potential in the facial nerve trunk, increased the thickness of the myelin sheath, and stimulated axon regeneration. CONCLUSION: Neuregulin-1 has the capability to facilitate the repair of facial nerve injuries by promoting the regenerative capacity of DPSCs. Thus, Neuregulin-1 is a significant potential gene in the reparative processes of nerve damage.

Integrated metabolomics and network pharmacology to reveal the lipid-lowering mechanisms of Qizha Shuangye granules in hyperlipidemic rats.

BACKGROUND: Qizha Shuangye granules (QSG) comprise six traditional Chinese herbal medicines (TCHMs), which have a long history of treating hyperlipidemia (HLP) in China. This study aimed to evaluate the potential lipid-lowering effects of QSG in an HLP rat model and investigate possible mechanisms. The HLP rat model was induced by a high-fat diet. Lipid-related indicators in serum were detected. Serum and liver metabolites were investigated using a liquid chromatography-mass spectrometry-based metabolomics approach. A herb-compound-target-metabolite (H-C-T-M) network was further constructed to reveal the possible molecular mechanism of QSG to alleviate HLP. RESULTS: The administration of QSG inhibited the HLP-induced changes in total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) levels. Additionally, QSG significantly attenuated the liver histopathological changes induced by HLP. Metabolomic analysis showed the serum and liver metabolic disorders presented in HLP rats. QSG can reverse the abnormal metabolism caused by HLP. Through network pharmacology analysis, key proteins such as androgen receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and peroxisome proliferator-activated receptor-α were screened out, and they were speculated to be possible therapeutic targets for QSG to treat HLP. CONCLUSION: The present study integrated metabolomics and network pharmacology analysis to reveal the efficacy and possible mechanism of QSG in treating HLP, which provides a new reference for the research and development of QSG as a functional food. © 2023 Society of Chemical Industry.

Multi-omics analysis of lung tissue metabolome and proteome reveals the therapeutic effect of Shegan Mahuang Decoction against asthma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan Mahuang Decoction (SMD) is a classic traditional Chinese medicine (TCM) formula for asthma treatment, but the anti-asthma mechanism of SMD is still not fully studied. AIMS OF THE STUDY: In this study, we established an ovalbumin (OVA)-induced asthma rat model and treated it with SMD to observe its anti-asthma effect and explore the related mechanism. MATERIALS AND METHODS: We evaluated the anti-inflammatory effect of SMD via testing the levels of immunoglobulin E (IgE), C-reactive protein (CRP), interleukin-4 (IL-4), interleukin-6 (IL-6) in serum and performing the hematoxylin-eosin (H&E) staining of lung tissue slices. We analyzed the variations of metabolites and proteins in the lung tissue of different groups using liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics and TMT-based proteomics approaches. The metabolic biomarkers and differentially expressed proteins (DEPs) were picked, and the related signal transduction pathways were also investigated. In addition, the key proteins on the signaling pathway were validated through western blotting (WB) experiment to reveal the anti-asthma mechanism of SMD. RESULTS: The results showed that the SMD could significantly reduce the serum levels of IgE, CRP, IL-4, and IL-6 and attenuate the OVA-induced pathological changes in lung tissue. A total of 34 metabolic biomarkers and 84 DEPs were screened from rat lung tissue, which were mainly associated with lipid metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, the excessive production of reactive oxygen species (ROS), and lysosome pathway. Besides, SMD could inhibit the myeloid differentiation factor 88 (MyD88)/inhibitor of kappa B kinase (IKK)/nuclear factor-kappa B (NF-κB) signaling pathway to exhibit anti-inflammatory activities. CONCLUSIONS: SMD exhibited a therapeutic effect on asthma, which possibly be exerted by inhibiting the MyD88/IKK/NF-κB signaling pathway.

Exploring the in vitro anti-inflammatory activity of gross saponins of Tribulus terrestris L. fruit by using liquid chromatography-mass spectrometry-based cell metabolomics approach.

Our previous studies confirmed the efficacy of gross saponins of Tribulus terrestris L. fruit in treating cerebral ischemia. This study aimed to investigate the related mechanisms in vitro. The lipopolysaccharide-induced BV2 cells model was constructed and treated with gross saponins at different concentrations to explore its anti-inflammatory activity. The cell metabolite changes were tracked by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, and the metabolic biomarkers and related metabolic pathways were analyzed. Molecular biochemistry analysis was further used to verify the relevant inflammatory pathways. The results showed that the saponins reduced nitric oxide release and the secretion of tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 from lipopolysaccharide-induced BV2 cells. Metabolic perturbations occurred in lipopolysaccharide-treated BV2 cells, which could be reversed by drug treatment via mainly regulating glycerophospholipid metabolism, tryptophan metabolism, purine metabolism pathways, etc. The western blot analysis demonstrated that saponin could suppress the activation of the inflammatory-related signaling pathway. The present study explored the in vitro anti-inflammatory mechanism of gross saponins of Tribulus terrestris L. fruit using an LC-MS-based cell metabolomics approach, which confirms the great potential of LC-MS for drug efficacy evaluation and can be applied in other herbal medicine-related analyses.

Dietary Supplement with Tribulus terrestris L. Extract Exhibits Protective Effects on Ischemic Stroke Rats.

SCOPE: Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear. METHODS AND RESULTS: The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL-6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF-κB signaling pathway. CONCLUSIONS: This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.

Application potential of biofertilizer-assisted Pennisetum giganteum in safe utilization of mercury-contaminated paddy fields.

High mercury (Hg) bioaccumulation in crops such as rice in Hg-contaminated areas presents a potential health hazard to humans and wildlife. To develop a safe alternative technique, bacillus-inoculated biofertilizer, citric acid, earthworms, and selenium-modified activated clay were compared for their ability to regulate Hg bioaccumulation in Pennisetum giganteum (P. giganteum). This biofertilizer significantly increased Bacillus sp. abundance in the soil by 157.12%, resulting in the removal of 27.52% of water-soluble Hg fractions through volatilization and adsorption mechanisms. The variation in bioavailable Hg in the soil significantly reduced the total Hg concentration in P. giganteum young leaves, old leaves, stems, and roots of P. giganteum by 74.14%, 48.08%, 93.72%, and 50.91%, respectively (p < 0.05), which is lower than the Chinese feed safety standard (100 ng g-1). The biofertilizer inhibitory potential was highly consistent with that of the selenium-modified activated clay. Biofertilizers significantly reduced the methylmercury concentration in various P. giganteum tissues (p < 0.05), whereas selenium-modified activated clay failed to achieve a comparable effect. This biofertilizer-assisted planting pattern can achieve an economic income quadruple that of the rice planting pattern in the Hg-contaminated paddy fields. Because of its significant environmental and financial applications, the biofertilizer-assisted planting pattern is expected to replace Hg-contaminated paddy fields.

Evaluation of allylestrenol for clinical pregnancies in patients treated with assisted reproductive techniques: a retrospective, propensity score matched, observational study.

BACKGROUND: Allylestrenol is an oral progestogen being increasingly used for luteal phase support in assisted reproductive techniques. However, evidence of the clinical efficacy of allylestrenol in luteal phase support is lacking. Dydrogesterone is a representative drug used for luteal phase support, the efficacy of which has been clinically confirmed. As such, we aimed to compare the effects of allylestrenol with the standard dydrogesterone on clinical pregnancy rates and pregnancy outcomes. METHODS: This retrospective study included 3375 assisted reproductive technique cycles using either allylestrenol or dydrogesterone between January 2015 and March 2020. Patients using either allylestrenol or dydrogesterone were matched in a 1:1 ratio using propensity scores. The primary outcomes were clinical pregnancy rate and pregnancy outcomes. RESULTS: No significant difference was found in the clinical pregnancy rate (53.5% vs. 53.2%, P = 0.928) and pregnancy outcomes (all P > 0.05) between allylestrenol and dydrogesterone. Compared with dydrogesterone, the use of allylestrenol significantly reduced the rate of biochemical pregnancies (6.4% vs. 11.8%, P < 0.001) and multiple gestation rate (16.8% vs. 26.3%, P = 0.001). Moreover, endometrial thickness, morphology, and blood flow were significantly improved by allylestrenol treatment (all P < 0.05). CONCLUSIONS: Allylestrenol exhibited similar effects on clinical pregnancy rates and pregnancy outcomes as dydrogesterone. Moreover, allylestrenol can significantly reduce the biochemical pregnancy rate and improve the endometrial receptivity.

Assessment of source-oriented health risk associated with the oral ingestion of heavy metals in dust within an iron/steel smelting-affected area of the North China Plain.

Heavy metals (HMs) from iron/steel smelting activities pose notable risks to human health, especially to those living around industrial facilities of North China Plain, the base of China's steel production. In this study, 78 outdoor windowsill dust samples were collected around a large-scale iron/steel smelter with more than 65 years of production history in the western North China Plain. Nine HMs were analysed to comprehensively assess the health risks by integrating Monte Carlo simulation, oral bioaccessibility, and source apportionment. Results showed serious pollution with Cd, Pb, and Zn based on their geo-accumulation index values and concentrations. Four potential sources including industrial sources (49.85%), traffic sources (21.78%), natural sources (20.58%), and coal combustion (7.79%) were quantitatively identified by multivariate statistical analysis. The oral bioaccessibilities of HMs determined by the physiologically based extraction test ranged from 0.02% to 65.16%. Zn, Mn, Cd, and Pb had higher bioaccessibilities than other HMs. After incorporating oral bioavailability adjustments, noncarcinogenic and carcinogenic risks were significantly reduced, especially for adults. The mean hazard index (HI) for children and adults was below the safety threshold (1.0), whereas the mean of the total carcinogenic risk (TCR) based on HM bioaccessibilities in the gastric phase remained above the acceptable level (1.0E-06) (children: 5.20E-06; adults: 1.16E-06). Traffic sources warranted increased concern as it substantially increased TCR. Cd was identified as the priority pollution in iron/steel smelting areas. Assessing source-oriented health risks associated with oral ingestion exposure can guide the management and control of HM contamination within iron/steel smelting-affected areas.

A practical method for the retrieval of tulip-head polyaxial pedicle screw by reusing the rod in revision and implants removal surgery: introduction of technique and evaluation of clinical outcomes.

BACKGROUND: The removal of spinal implants is needed in revision surgery or in some cases whose fracture had healed or fusion had occurred. The slip of polyaxial screw or mismatch of instruments would make this simple procedure intractable. Here we introduce a simple and practical method to address this clinical dilemma. METHODS: This is a retrospective study. The patients underwent new technique for retrieving the implants from July 2019 to July 2022 were labeled as group A, while the patients underwent traditional implants retrieval technique from January 2017 to January 2020 were labeled as group B. Patients in each group were subdivided into revision surgery group (r group) and simple implants removal group (s group) according to the surgery fashion. For the new technique, the retrieved rod was cut off to a proper length which was matched with the size of tulip head, and was replaced into the tulip head. After tightened with nut, a monoaxial screw-rod "construct" was formed. Then the "construct" can be retrieved by a counter torque. The operation duration, intraoperative blood loss, post-operative bacteria culture, hospital stay and costs were analyzed. RESULTS: A total of 116 polyaxial screws with difficult retrieval (43 screws in group A, 73 screws in group B) in 78 patients were recorded, in which 115 screws were successfully retrieved. Significant differences were found in the mean operation duration, intraoperative blood loss when comparing the r group in group A and B, as well as the s group in group A and B (P < 0.05). There were no significant differences in hospital stay and costs between group A and B. Three patients were found positive bacteria culture of drainage tube/tape in group A (3/30), while 7 patients in group B (7/48). The most prevalent bacteria was Propionibacterium acnes. CONCLUSION: This technique is practical and safe in retrieving tulip head poly-axial screw. Reduced operation duration and intraoperative bloods loss may potentially alleviate the hospitalization burden of patients. Positive bacterial cultivation results are common after implants removal surgery, but they rarely represent an organized infection. A positive culture with P. acnes or S. epidermidis should be interpreted with caution.

Aquatic methylmercury is a significant subsidy for terrestrial songbirds: Evidence from the odd mass-independent fractionation of mercury isotopes.

In contrast to aquatic food chains, knowledge of the origins and transfer of mercury (Hg) and methylmercury (MeHg) in terrestrial food chains is relatively limited, especially in songbirds. We collected soil, rice plants, aquatic and terrestrial invertebrates, small wild fish, and resident songbird feathers from an Hg-contaminated rice paddy ecosystem for an analysis of stable Hg isotopes to clarify the sources of Hg and its transfer in songbirds and their prey. Significant mass-dependent fractionation (MDF, δ202Hg), but no mass-independent fractionation (MIF, ∆199Hg) occurred in the trophic transfers in terrestrial food chains. Piscivorous, granivorous, and frugivorous songbirds and aquatic invertebrates were all characterized by elevated Δ199Hg values. The estimated MeHg isotopic compositions obtained using linear fitting and a binary mixing model explained both the terrestrial and aquatic origins of MeHg in the terrestrial food chains. We found that MeHg from aquatic habitats is an important subsidy for terrestrial songbirds, even those that feed mainly on seeds, fruits, or cereals. The results show that MIF of the MeHg isotope is a reliable tool to reveal MeHg sources in songbirds. Because the MeHg isotopic compositions was calculated with a binary mixing model or directly estimated from the high proportions of MeHg, compound-specific isotope analysis of Hg would be more useful for the interpretation of the Hg sources, and is highly recommended for future studies.

VEGFA-modified DPSCs combined with LC-YE-PLGA NGCs promote facial nerve injury repair in rats.

Objective: The aim of this research was to investigate the effect of vascular endothelial growth factor A (VEGFA)-overexpressing rat dental pulp stem cells (rDPSCs) combined with laminin-coated and yarn-encapsulated poly(l-lactide-co-glycolide) (PLGA) nerve guidance conduit (LC-YE-PLGA NGC) in repairing 10 mm facial nerve injury in rats. Study Design: rDPSCs isolated from rat mandibular central incisor were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-VEGFA). To investigate the role and mechanisms of VEGFA in neurogenic differentiation in vitro, semaxanib (SU5416), Cell Counting Kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed. Ten-millimeter facial nerve defect models in rats were established and bridged by LC-YE-PLGA NGCs. The repair effects were detected by transmission electron microscopy (TEM), compound muscle action potential (CMAP), immunohistochemistry and immunofluorescence. Results: Extracted cells exhibited spindle-shaped morphology, presented typical markers (CD44+CD90+CD34-CD45-), and presented multidirectional differentiation potential. The DPSCs with VEGFA overexpression were constructed successfully. VEGFA enhanced the proliferation and neural differentiation ability of rDPSCs, and the expression of neuron-specific enolase (NSE) and ßIII-tubulin was increased. However, these trends were reversed with the addition of SU5416. This suggests that VEGFA mediates the above effects mainly through vascular endothelial growth factor receptor 2 (VEGFR2) binding. The LC-YE-NGC basically meet the requirements of facial nerve repair. For the in vivo experiment, the CMAP latency period was shorter in DPSCS-VEGFA-NGC group in comparison with other experimental groups, while the amplitude was increased. Such functional recovery correlated well with an increase in histological improvement. Further study suggested that VEGFA-modified DPSCs could increase the myelin number, thickness and axon diameter of facial nerve. NSE, ßIII-tubulin and S100 fluorescence intensity and immunohistochemical staining intensity were significantly enhanced. Conclusion: VEGFA-modified rDPSCs combined with LC-YE-PLGA NGCs have certain advantages in the growth and functional recovery of facial nerves in rats.

Human Dietary Exposure to Heavy Metals via Rice in Nepal.

The effects of exposure to heavy metals (HMs) in rice on human health have become a global public health concern, particularly in countries where rice is consumed as a staple food. The concentrations of HMs, including cadmium (Cd), arsenic (As), lead (Pb), and copper (Cu), in commercial rice samples (n = 170) were analyzed to estimate the HM exposure of consumers in Nepal. The geometric mean concentrations of Cd, As, Pb, and Cu in commercial rice were 15.5 ± 16.0, 43.4 ± 19.6, 16.0 ± 14.0, and 1066 ± 1210 µg/kg, respectively, all below the maximum allowable concentrations (MACs) recommended by FAO/WHO. Generally, the average estimated daily intakes (EDIs) of Cd, As, Pb, and Cu were all below the oral reference doses (RfDs). However, young age groups were exposed to high levels of HMs, and the average EDI of As and the P99.9 EDIs of Cu and Cd were above the corresponding RfDs. The mean hazard index and total carcinogenic risk were 1.13 and 1.04 × 10-3 respectively, suggesting a potential non-carcinogenic risk (NCR) and a carcinogenic risk (CR) via rice consumption. Arsenic contributed the most strongly to NCR and Cd to CR. Overall, although the HM levels in rice were generally safe, the Nepalese population may be exposed to an elevated health risk from rice consumption.

Investigating the in vivo effect of Tribulus terrestris extract in middle cerebral artery occlusion rats using LC-MS-based metabolomics combined with molecular docking.

Tribulus terrestris L. fruit (TT) is a traditional Chinese herbal medicine used to treat ischemic stroke (IS). This study aimed to investigate the protective effect of TT extract, named TT15, on middle cerebral artery occlusion (MCAO) rats using metabolomics and molecular docking and find the targets of action and the material basis of TT15 against IS. The results of the infarct volume and neurological defect scores confirmed the efficacy of TT15. Serum metabolomics analysis using LC-MS revealed that model group animals experienced a variety of metabolic disturbances when compared to the sham group. TT15 can restore the MCAO-induced serum metabolite changes by modulating multiple metabolic pathways. Six enzymes were highlighted by the metabolite-reaction-enzyme-gene (M-R-E-G) network analysis, which might be the possible targets for the TT15 against IS. Molecular docking analysis was applied to show the binding affinities between active compounds and these enzymes. The representative docking mode with the lowest binding energy between three compounds and phospholipase A 2 (PLA2) and peroxidase (POD) was displayed by the ribbon binding map. This study profiles the metabolic changes in MCAO-induced IS and investigates the efficacy and the corresponding mechanism of TT15 in the treatment of IS.

Health risk assessment of heavy metals in road dust from the fourth-tier industrial city in central China based on Monte Carlo simulation and bioaccessibility.

Health risks caused by heavy metal (HM) exposure in road dust has attracted extensive attention, but few studies have focused on the health risks of residents living in small- and medium-sized cities with rapid industrialization and urbanization. Thus, 140 road dust samples were collected across Anyang, a typical fourth-tier industrial city in central China, which were analysed for 10 different HMs (Mn, Zn, Pb, V, Cr, As, Cd, Ni, Cu and Co). Monte Carlo simulation and bioaccessibility were used to quantify the health risks of heavy metals comprehensively in road dust. Results revealed a remarkable accumulation of Mn, Zn, Pb, Cd and Cu. According to the Geo-accumulation index and potential ecological risk index, Cd was priority control pollutant. Moreover, 55.0% of the road dust samples reached heavily polluted level, and 52.86% of the samples were at high ecological risk levels. These results illustrated that HM contamination was serious and universal in the road dust of Anyang. The occurrences of HMs were allocated to traffic emissions, natural sources, industrial activities and agricultural activities with contribution rates of 35.4%, 6.0%, 41.6% and 17.0%, respectively. Except for Zn in the gastric phase, all other HMs had relatively low bioaccessibilities in the gastrointestinal system, usually less than 20%. The bioaccessibilities of most HMs were higher in the gastric phase, except for Cr, Ni and Cu, which remained higher in the intestinal phase. The non-carcinogenic risk and carcinogenic risk were remarkably reduced when considering the HM bioaccessibilities in the gastrointestinal system, especially for adults. The outcomes of this paper are valuable for understanding HM contamination in road dust and highlight the importance of risk assessment for populations living in the fourth- and fifth-tier cities.

Isopsoralen suppresses receptor activator of nuclear factor kappa-ß ligand-induced osteoclastogenesis by inhibiting the NF-κB signaling.

Osteoporosis is a serious systemic metabolic bone system disease.This study aimed to identify the target genes of isopsoralen and the signaling pathways involved in the differential expression of the genes involved in osteoclast differentiation. We hypothesized that isopsoralen may inhibit osteoclast differentiation by blocking the nuclear factor kappa-B (NF-κB) signaling pathway and verified our hypothesis through basic experiments. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to detect the effect of isopsoralen on the proliferation and viability of primary mouse bone marrow monocytes (BMMCs). The effect of isopsoralen on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation was determined by using tartrate-resistant acid phosphatase (TRAP) staining. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of the related genes and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of isopsoralen target genes were obtained through comprehensive analysis using the STITCH database, Cytoscape 3.8.2, and R-Studio software. Differentially expressed genes (DEGs) were found in osteoclasts induced by RANKL before and after 3 days using R-Studio, following which KEGG analysis was performed. Next, enrichment analysis was performed on the KEGG pathway shared by the target genes of isopsoralen and the differentially expressed genes during osteoclast differentiation to predict the signaling pathway underlying the inhibition of osteoclast differentiation by isopsoralen. Finally, Western blot was used to detect the effect of isopsoralen on the activation of signaling pathways to verify the results of our bioinformatics analysis. Based on the enrichment analysis of isopsoralen target genes and differentially expressed genes during osteoclastogenesis, we believe that isopsoralen can inhibit RANKL-induced osteoclastogenesis by inhibiting the NF-κB signaling pathway.