Inositol-requiring enzyme 1α and c-Jun N-terminal kinase axis activation contributes to intracellular lipid accumulation in calf hepatocytes.

During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content <1%) and 10 cows with fatty liver (hepatic TG content >5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and ß-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30-40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

A grading system for evaluation of bladder trabeculation.

PURPOSE: To establish a parameter-based grading system for evaluating bladder trabeculation (BT). MATERIALS AND METHODS: A retrospective analysis was conducted on children diagnosed with posterior urethral valve (PUV) or neurogenic bladder (NB) who underwent voiding cystourethrogram (VCUG), urodynamic testing, and urological ultrasonography between January 2016 and October 2022. Cases involving urologic surgery, secondary bladder pathology, and an interval of more than 12 months between examinations were excluded. A parameter named Bladder Dispersion (BD) was calculated through fluoroscopic images, and the grading system was developed as follows: BD < 40 (Grade 0), 40 ≤ BD < 60 (Grade 1), 60 ≤ BD < 90 (Grade 2), BD ≥ 90 (Grade 3). Grades 0-1 were classified as low-risk group, while grades 2-3 were classified as high-risk group. Analysis of variance, Kruskal-Wallis test, and Chi-square test were performed to compare urodynamic results and complications across different grades and groups. RESULTS: A total of 74 patients were eligible to participate, which included 46 boys (62.2%) and 28 girls (37.8%), the mean age was 75.18 ± 48.39 months. Among them, 11 (14.9%) were PUV, 50 (67.6%) were NB, and 13 (17.5%) were PUV and NB. Significant differences were observed in maximum detrusor pressure, post-void residual urine ratio, and compliance among grades 0-3. Severe hydronephrosis and histories of urinary tract infection were more prevalent in the high-risk group. CONCLUSION: A reliable grading system with objective standards was proposed which could aid in the assessment of BT severity.

The Effect of Psychological Intervention on the Visual Quality of Patients with a Diffractive Multifocal Intraocular Lens Implant.

OBJECTIVE: This study aimed to investigate the effect of psychological intervention on the visual quality of patients with a diffractive multifocal intraocular lens implant and its possible mechanism. METHODS: Eighty-nine patients undergoing age-related cataract surgery were enrolled in the study at the Affiliated Hospital of Southwest Medical University between December 2015 and July 2017. They were randomly divided into two groups: multiple focus M1 group (n = 45) and multiple focus M2 group (n = 40). The M1 group was only given routine preoperative health education, treatment, and evaluation, while the M2 group also received psychological intervention. RESULTS: After treatment, there was no statistical difference in the uncorrected distance and near visual acuity, corrected distance and near visual acuity, or the vision and near removal rate in either of the two groups (p > 0.05). However, postoperative glare was lower in the M2 group (p < 0.05), and patient satisfaction was higher in the M2 group (p < 0.05). The M2 group had a more obvious improvement in the Symptom Checklist-90 score (p < 0.05), the serum interleukin-6 (IL-6) was lower, and the serum brain-derived neurotrophic factor (BDNF) was higher in the M2 group (p < 0.05). In addition, serum IL-6 had a negative correlation with the depression score, and serum BDNF also showed a negative correlation with the anxiety score (p < 0.05). CONCLUSIONS: Psychological intervention improved the stress state of patients with age-related cataracts and diffractive multifocal intraocular lens implants, reduced the level of inflammatory factors in the body, improved the level of BDNF, reduced postoperative visual interference, and improved postoperative satisfaction.

Dietary Fiber and Human Papillomavirus Infection among US Women: The National Health and Nutrition Examination Survey, 2003-2016.

The impact of dietary fiber on human papillomavirus (HPV) infection is still underway. The aim of our study was to investigate the association between intake of dietary fiber and HPV infection. Overall, 14,151 eligible women, aged 18-59 years old, who submitted an adequate sample for HPV test, were collected from an ongoing, large scale population-based survey for seven cycles. The association of dietary fiber intake and HPV infection was assessed in multivariate logistic models. For sensitivity analysis, generalized additive model (GAM) and smooth curve fitting were employed to verify the robustness of the results. Among 14,151 eligible participants, intake of dietary fiber was negatively associated with HPV infection. Each additional increase in log10 dietary fiber consumption was associated with a 57% lower risk of HPV infection (OR, 0.43; 95% CI 0.38-0.48). The result is stable in minimally and fully adjusted model. The possibility of nonlinear association of dietary fiber and HPV infection has been excluded by GAM and smooth curve fitting. There was an inverse linear correlation between intake of dietary fiber and HPV infection. Our findings obtained from NHANES dataset suggested that increasing dietary fiber consumption may be associated with the prevalence of HPV infection.

A novel ZnCo2O4/BiOBr p-n/Z-scheme heterojunction photocatalyst for enhancing photocatalytic activity.

In this study, we developed a novel p-n/Z-scheme heterojunction photocatalyst, ZnCo2O4/BiOBr (ZCo/BB), through a straightforward and safe hydrothermal-calcination-solvent thermal method. The composite photocatalyst demonstrated exceptional photocatalytic efficacy, particularly when the mass ratio of ZnCo2O4 was 25% (referred to as 25% ZCo/BB). Structural characterization and electrochemical analysis revealed that 25% ZCo/BB exhibited a larger specific surface area and a faster electron transfer rate. Under visible light exposure for 30 min, methylene blue (MB) degradation reached 92%, and the reaction rate constants were 8.2 and 3.7 times higher than those observed for individual ZnCo2O4 and BiOBr, respectively. Furthermore, the 25% ZCo/BB demonstrated exceptional photocatalytic stability over four cycles, maintaining over 80% MB degradation after each cycle. The outstanding photocatalytic activity was attributed to the p-n/Z-scheme heterojunction construction, which promoted charge separation and inhibited carrier recombination. In addition, ·OH and h+ were the major active species in photocatalysis, and · O 2 - was identified as a secondary active species. This work presents an efficient heterojunction photocatalyst for the degradation of organic wastewater.

Preparation of medium- and long-chain triacylglycerols rich in n-3 polyunsaturated fatty acids by bio-imprinted lipase-catalyzed interesterification.

Medium and long-chain triacylglycerol (MLCT) rich in n-3 polyunsaturated fatty acids (PUFAs) were obtained in three-hour interesterification of fish oil with medium-chain triacylglycerol (MCTs), using lipase bio-imprinted with surfactant as a catalyst. Initially, for bio-imprinted lipase preparation, the interesterification reaction conditions were optimized, resulting in a lipase with 1.47 times higher catalytic activity compared to control (non-bio-imprinted). Afterwards, the reaction conditions for MLCT synthesis were optimized, using bio-imprinted lipase as a catalyst. The reaction reached equilibrium within first three hours at 70 °C temperature, 4 wt% lipase load, and molar ratio of substrate 1:1.5. Under these conditions, final product contained 18.52% MCT, 56.65% MLCT, and 24.83% long-chain triacylglycerol (LCT). To reduce the MCT content, a solvent extraction process was performed, yielding 2.42% MCT, 56.19% MLCT, and 41.39% LCT. The obtained structured lipids (SLs), enriched in n-3 PUFAs, offer significant health benefits, enhanced bioavailability, with potential applications in functional foods and nutraceuticals.

Analysis of Clinical and Microbiological Features of Listeria monocytogenes Infection.

Introduction: To analyze the demographics and clinical features of 59 cases of Listeria monocytogenes, and determine the predisposing conditions for severe meningitis infections for reference. Materials and methods: A total of 59 cases isolated L. monocytogenes from 2009 to 2020 were enrolled. Electronic medical record data were used to determine the epidemiological and clinical characteristics of L. monocytogenes infection. Univariate and multifactorial logistic regression analyses were performed to predict risk factors for Listeria meningitis. Results: A total of 59 cases (median age of 52 years, 30 females and 29 males) were enrolled. Twenty-five patients (42.37%) developed a neuroinvasive infection. The indexes of interleukin-6 (IL-6), CD3+T, CD4+T, and CD8+T cells in the study group were higher than those in the control group (P<0.05). In univariate analysis, the use of hormone drugs (odds ratio=3.21, P=0.000) and immunosuppressive agents (odds ratio=3.06, P=0.000) were relevant predictors of severe meningitis. 47 patients (79.66%) were treated with ampicillin (27.12%), carbapenems (18.64%), quinolones (11.86%), and ß-lactamase inhibitors (11.86%) as the primary agents of antimicrobial therapy. Thirty-four patients (57.63%) showed clinical improvement, five patients (8.47%) had a poor prognosis, and two patients (3.39%) died. Conclusion: Infection with Listeria changed the levels of IL-6, CD3+T, CD4+T, and CD8+T cells, and these analyzing items were significantly different between L. monocytogenes and other bacterial infections. Long-term use of immunosuppressants and hormones may be risk factors for severe adult forms of Listeria-related infections. Sensitive antibiotics, such as penicillins and carbapenems, should be added or replaced in the early empiric treatment of L. monocytogenes.

Circ_0080940 Regulates miR-139-5p/CTGF Pathway to Promote the Proliferation, Migration, Extracellular Matrix Deposition of Human Tenon's Capsule Fibroblasts.

PURPOSE: Circular RNA (circRNA) has been identified as an important regulator for glaucoma progression. Our study aims to reveal the circ_0080940 roles in glaucoma progression. METHODS: Transforming growth factor ß1 (TGF-ß1) was used to treat human Tenon's capsule fibroblasts (HTFs) to mimic glaucoma cell models. Cell function was determined by cell counting kit 8 assay, EdU assay and wound healing assay. Protein levels were determined by western blot analysis. Quantitative real-time PCR was used to measure RNA expression. Dual-luciferase reporter assay was performed to evaluate RNA interaction. RESULTS: Our data confirmed that TGF-ß1 induced HTFs proliferation, migration and extracellular matrix (ECM) deposition. Circ_0080940 was highly expressed in glaucoma patients, and its knockdown inhibited TGF-ß1-induced proliferation, migration and ECM deposition in HTFs. Circ_0080940 sponged miR-139-5p, and anti-miR-139-5p revoked the effect of si-circ_0080940 on the biological functions of TGF-ß1-induced HTFs. CTGF was targeted by miR-139-5p, and overexpressed CTGF overturned the inhibition effect of miR-139-5p on the biological functions of TGF-ß1-induced HTFs. Furthermore, CTGF expression could be positively regulated by circ_0080940. CONCLUSION: To sum up, we confirmed that circ_0080940 contributed to glaucoma progression by miR-139-5p/CTGF axis.

MicroRNA-93 promotes the pathogenesis of glaucoma by inhibiting matrix metalloproteinases as well as up-regulating extracellular matrix and Rho/ROCK signaling pathways.

Objective: To investigate the effect and potential molecular mechanism of microRNA-93 (miR-93) on retinal ganglion cells (RGCs) apoptosis as well as retinal damage in acute glaucoma mice. Methods: RGCs apoptosis were induced by oxygen-glucose deprivation and reperfusion (OGD/R). The pro-apoptotic effect of miR-93 was evaluated by transfecting miR-93 mimics or miR-93 inhibitor into OGD/R-induced RGCs. The viability and apoptosis of RGCs were determined by MTT assay and flow cytometry. Mouse model of acute glaucoma were successfully induced via high intraocular pressure (IOP), and then these model animals were randomly divided into vehicle group, miR-93 mimics group or miR-93 inhibitor group (n = 10), using healthy mice as normal control. Histopathologic changes of retinal tissue were evaluated by Hematoxylin and Eosin (H&E) staining method. Moreover, cell counts of retinal ganglion cell layer and mean thickness of different layers were also determined. Quantitative real-time PCR (qPCR) and western blotting analysis were used to detect the mRNA and protein expression levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and Rho/ROCK signaling pathway. Results: miR-93 mimics significantly decreased or promoted the viability and apoptosis of OGD/R-induced RGCs, respectively. In addition, miR-93 mimics significantly exacerbated the degree of retinal tissue damage in mice with acute glaucoma, which was accompanied by a decrease in the number of ganglion cell layer (GCL) cells and the thickness of different tissue layers. Moreover, miR-93 mimics significantly increased IOP in mice with acute glaucoma. Significantly, miR-93 inhibitors significantly reversed the above changes. In addition, results of Western blot analysis showed that miR-93 mimics increased and decreased the expression of ECM-associated and MMP-associated proteins, respectively, by activating the Rho/ROCK signaling pathway. In contrast, miR-93 significantly decreased and increased the expression of ECM-associated and MMP-associated proteins, and suppressed the expression of Rho/ROCK signaling pathway-related proteins. Conclusion: miR-93 can promote the development of glaucoma by activating Rho/ROCK signaling pathway to mediate the accumulation of ECM-related proteins as well as the down-regulation of MMP-related proteins.

Efficacy of Body Wash and Povidone-Iodine in Skin Preparation in Reducing Surgical Site Infections After Hypospadias Repair Among Adolescents: A Prospective Cohort Study With Retrospective Controls.

Background: Surgical site infections (SSIs) that occur after hypospadias repair frequently result in incision healing complications, especially during puberty. This study aimed to evaluate the efficacy of twice-daily pre-operative skin preparation using body wash and povidone-iodine within 48 hours before hypospadias repair with regard to infection rates in adolescents. Patients and Methods: Prospective recruitment included patients in Tanner stages 3 to 5 undergoing hypospadias repair from January 2015 to January 2021. The experimental group comprised patients who performed twice-daily skin preparation with body wash and povidone-iodine within 48 hours before surgery. Surgeons selected either 0.5% or 5% povidone-iodine for skin preparation. The control group comprised a retrospective cohort of hypospadias repair conducted in the preceding five years, where patients performed pre-surgery evening showers using a body wash. Complications were collected over a six-month follow-up period. Results: The study included 90 patients in the 0.5% povidone-iodine group, 92 patients in the 5% povidone-iodine group, and 84 patients in the control group. Differences were observed among the groups in terms of SSI (p = 0.030) and urethral fistula (p = 0.019). In post hoc tests, only the 5% povidone-iodine group demonstrated a diminished incidence of SSI (p = 0.009) and urethral fistula (p = 0.005) in comparison to the control group. Conclusions: Using body wash and 5% povidone-iodine for skin preparation was associated with a reduction in the incidence of SSI and urethral fistula following hypospadias repair in adolescents and may be considered to improve outcomes.

The Effect and the Mechanism of Comprehensive Treatment on the Ocular Surface and the Visual Quality of Online Teachers with a Mild-to-Moderate Dry Eye Condition During the Early Phase of Coronavirus Disease 2019.

OBJECTIVE: To investigate the effect of comprehensive treatment on ocular surface function and the visual quality of online teachers with a mild-to-moderate dry eye condition during the early phase of coronavirus disease 2019 (COVID-19). METHODS: Secondary school online teachers diagnosed with a mild-to-moderate dry eye disease in our outpatient clinic from February to May 2020 were enrolled in this retrospective cross-section study, and all patients received dry eye comprehensive treatment. A questionnaire survey on eye-use habits, visual quality and dry eye-related indicators was collected before and after treatment (2 and 4 weeks). The changes and the correlations between indicators before and after treatment were compared. RESULTS: A total of 30 patients (15 females and 15 males) were included. After comprehensive treatment, patients had significantly higher central tear meniscus height (TMH), non-invasive first tear film breakup time (NIBUTf) and non-invasive average tear film breakup time (NIBUTav) than those before with statistical significance (P < 0.05). Lower ocular surface disease index (OSDI) and Meibomian gland scores were observed after treatment with statistical significance (P < 0.05). Objective scatter index (OSI), modulation transfer function (MTF) cutoff, strehl ratio (SR), and tear film objective scatter index (TF-OSI) were significantly improved after treatment (P < 0.05). Besides, TF-OSI was positively correlated with the changes in OSDI, Meibomian gland score, eye-use duration and OSI with statistical significance (P < 0.05), while it was negatively correlated with NIBUTf, NIBUTav, the TMH of the central lower eyelid, SR, sleep duration, conjunctival congestion and the MTF cutoff (P < 0.05), respectively. No correlation between TF-OSI and ciliary congestion was found (P > 0.05). CONCLUSION: Comprehensive treatment could effectively improve the symptoms and visual quality of online teachers with a mild-to-moderate dry eye condition during the early stage of COVID-19 pandemic.

Using ROPScore and CHOP ROP for early prediction of retinopathy of prematurity in a Chinese population.

PURPOSE: Retinopathy of prematurity (ROP) is a disease that causes vision loss, vision impairment, and blindness, most frequently manifesting among preterm infants. ROPScore and CHOP ROP (Children's Hospital of Philadelphia ROP) are similar scoring models to predict ROP using risk factors such as postnatal weight gain, birth weight (BW), and gestation age (GA). The purpose of this study was to compare the accuracy and difference between using ROPScore and CHOP ROP for the early prediction of ROP. METHODS: A retrospective study was conducted from January 2009 to December 2019 in China. Patients eligible for enrollment included infants admitted to NICU at ≤32 weeks GA or those with ≤1500 g BW. The sensitivity and specificity of ROPScore and CHOP ROP were analyzed, as well as its suitability as an independent predictor of ROP. RESULTS: Severe ROP was found in 5.0% of preterm infants. The sensitivity and specificity of the ROPScore test at any stage of ROP was 55.8 and 77.8%, respectively. For severe ROP, the sensitivity and specificity was 50 and 87.0%, respectively. The area under the receiver operating characteristic curve for the ROPScore for predicting severe ROP was 0.76. This value was significantly higher than the values for birth weight (0.60), gestational age (0.73), and duration of ventilation (0.63), when each was category measured separately. For the CHOP ROP, it correctly predicted infants who developed type 1 ROP (sensitivity, 100%, specificity, 21.4%). CONCLUSIONS: The CHOP ROP model predicted infants who developed type 1 ROP at a sensitivity of 100% whereas ROPScore had a sensitivity of 55.8%. Therefore, the CHOP ROP model is more suitable for Chinese populations than the ROPScore test. CLINICAL REGISTRATION NUMBER AND STROBE GUIDELINES: This article was a retrospective cohort study and reported the results of the ROPScore and CHOP ROP algorithms. No results pertaining to interventions on human participants were reported. Thus, registration was not required and this study followed STROBE guidelines.

MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high fatality rate in men and women worldwide. Recently, microRNAs (miRNAs) have been reported to be diagnostic biomarkers and therapeutic targets in NSCLC. MiR-223-3p was proved to act as a promoter in NSCLC progression. However, the regulatory mechanism of miR-223-3p in NSCLC remains little known. This study aimed to explore the regulatory mechanism between miR-223-3p and its target gene Ras homolog family member B (RHOB) in NSCLC. The mRNA level of miR-223-3p and RHOB was measured by quantitative reverse transcription PCR. Furthermore, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was conducted to analyze cell apoptosis. Transwell assays and wound healing assay were employed to examine migration and invasion. The target relationship between miR-223-3p and RHOB was predicted by starBase online database and verified by dual-luciferase assay. The protein level of RHOB was tested by western blot. Our data suggested that miR-223-3p was upregulated in NSCLC tissues and cell lines and high level of miR-223-3p contributed to a poor survival in NSCLC patients. Knockdown of miR-223-3p exerted inhibitory effects on NSCLC cell viability, migration, and invasion and promotion effect on cell apoptosis. Furthermore, RHOB was directly targeted by miR-223-3p and constrained NSCLC progression. Moreover, knockdown of RHOB rescued the effect of anti-miR-223-3p on NSCLC progression. In vivo experiments indicated that miR-223-3p deletion suppressed tumor growth. MiR-223-3p could regulate the NSCLC cellular processes through targeting RHOB.

Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways.

OBJECTIVE: Genistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes. MATERIALS AND METHODS: HeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 µM, 12.5 µM, 25 µM, 50 µM and 100 µM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 µM genistein, the migration ability was detected by the scratch assay. Transwell assay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively. RESULTS: The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 µM. After treatment with 100 µM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 µM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist. CONCLUSION: Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.

Shikonin suppresses trophoblast cell growth via regulation of GLI1, and p62 mediated caspase 8 activation.

Unruptured ectopic pregnancy (UEP) is a common cause of morbidity and, occasionally, of mortality in women of reproductive age. Pharmacological intervention is a common therapeutic approach for early-stage UEP. Herein, we investigated the cytotoxic effect and novel mechanism of shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, in human trophoblast cells. These data demonstrated that shikonin suppressed proliferation and induced apoptosis in a time-dependent manner in HTR-8/SVneo cells. Shikonin blocked autophagic flux and promoted p62 interaction with caspase 8, resulting in caspase 8 activation. Moreover, shikonin suppressed GLI1 expression, and GLI1 overexpression attenuated shikonin-induced cell apoptosis. Although silencing GLI1 slightly promoted cell apoptosis, p62 overexpression enhanced GLI1 silencing-induced cell apoptosis by activating caspase 8. Furthermore, rapamycin increased shikonin-induced cell apoptosis in HTR-8/SVneo cells, whereas 3-MA attenuated the cytotoxic effect of shikonin. In conclusion, shikonin suppressed trophoblast cell growth by silencing GLI1 and increasing p62 co-mediated activation of caspase 8, which suggested a potential novel therapeutic target for UEP.

Elevated blood mercury level has a non-linear association with infertility in U.S. women: Data from the NHANES 2013-2016.

Mercury is a ubiquitous toxic heavy metal associated with an increased risk of female infertility; however, the evidence supporting this is limited and controversial. We aimed to explore the relationship between the total blood mercury and infertility in 1796 selected participants from the National Health and Nutrition Examination Survey (NHANES) (2013-2016). We found no significant association between mercury and infertility based on a fully-adjusted model (OR 1.04; 95 % CI 0.91, 1.19), and the results remained robust in a series of sensitive analysis. However, a non-linear relationship was detected. By a two-piecewise linear regression model and recursive algorithm, we identified an inflection point of 5.278 µg/L, when blood mercury was >5.278 µg/L, a 1-unit increase in mercury (log2) was associated with 157 % greater adjusted odds of infertility (OR 2.57; 95 % CI 1.12, 5.87). Our findings provide new insights to advance the research of the link between mercury and infertility.

A new neolignan from the thorns of Gleditsia japonica var. delavayi.

A new neolignan, 5-(3″-acetoxypropyl)-2-(4'-hydroxy-3'-methoxyphenyl)-7-methoxy-3-methylbenzofuran (1) along with nine analogues were isolated from the thorns of Gleditsia japonica var. delavayi by solvent extraction and repeated column chromatography. Their structures were elucidated by means of extensive spectroscopic analysis including 1D, 2D-NMR techniques and HR-ESIMS. All the isolates were reported for the first time from this species.