ASIC1a regulates ferroptosis in hepatic stellate cells via the Hippo/Yap-1 pathway in liver fibrosis.

BACKGROUND: Liver fibrosis is a sustained process of liver tissue damage and repair caused by various physiological and pathological factors, with the activation and proliferation of hepatic stellate cells being central. Therefore, understanding and clarifying the relevant mechanisms of hepatic stellate cell activation and death is of great clinical significance for the treatment of liver fibrosis diseases. METHODS: In vivo, recombinant adeno-associated virus was used to infect the liver of experimental mice, overexpressing ASIC1a, and based on this, a liver fibrosis model treated with sorafenib was constructed. In vitro, using RNA plasmid technology to transfect HSC-T6 cells, ASIC1a was overexpressed or silenced in the cells, and on this basis, PDGF-BB and Sorafenib were used to stimulate HSC-T6 cells, causing activated HSC-T6 to undergo ferroptosis. RESULTS: The ferroptosis inducers Sorafenib and erastin can induce ferroptosis in HSCs, effectively inhibiting or reversing the progression of liver fibrosis. We found that the expression level of ASIC1a was significantly reduced in the livers of mice with liver fibrosis treated with Sorafenib. After treatment with an adeno-associated virus overexpressing ASIC1a, the therapeutic effect of Sorafenib was inhibited, and the level of ferroptosis induced by Sorafenib was also inhibited. The induction of ferroptosis in hepatic stellate cells in vitro depends on the presence of ASIC1a. By further exploring the potential mechanism, we observed that the overexpression of ASIC1a can promote an increase in YAP nuclear translocation, thereby regulating the activity of Hippo/YAP pathway signaling. After treatment with Sorafenib, the influx of Ca2+ significantly increased when ASIC1a was overexpressed, and BAPTA-AM intervention eliminated the intracellular Ca2+ accumulation induced by ASIC1a overexpression. CONCLUSIONS: This indicated that the activation of YAP depends on the calcium ion influx induced by ASIC1a, which regulates ferroptosis in hepatic stellate cells by regulating the calcium ion-dependent Hippo/YAP pathway.

Targeted long-read sequencing identifies missing pathogenic variant in unsolved 11ß-hydroxylase deficiency.

BACKGROUND: 11ß-hydroxylase deficiency (11ß-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11ß-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11ß-OHD. METHODS: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. RESULTS: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269-143,957,579 (hg19) with the insertion of 'ACAG' (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. CONCLUSIONS: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11ß-OHD genetic diagnosis and carrier sequencing.

KIAA0753 enhances osteoblast differentiation suppressed by diabetes.

Diabetes-related bone loss represents a significant complication that persistently jeopardizes the bone health of individuals with diabetes. Primary cilia proteins have been reported to play a vital role in regulating osteoblast differentiation in diabetes-related bone loss. However, the specific contribution of KIAA0753, a primary cilia protein, in bone loss induced by diabetes remains unclear. In this investigation, we elucidated the pivotal role of KIAA0753 as a promoter of osteoblast differentiation in diabetes. RNA sequencing demonstrated a marked downregulation of KIAA0753 expression in pro-bone MC3T3 cells exposed to a high glucose environment. Diabetes mouse models further validated the downregulation of KIAA0753 protein in the femur. Diabetes was observed to inhibit osteoblast differentiation in vitro, evidenced by downregulating the protein expression of OCN, OPN and ALP, decreasing primary cilia biosynthesis, and suppressing the Hedgehog signalling pathway. Knocking down KIAA0753 using shRNA methods was found to shorten primary cilia. Conversely, overexpression KIAA0753 rescued these changes. Additional insights indicated that KIAA0753 effectively restored osteoblast differentiation by directly interacting with SHH, OCN and Gli2, thereby activating the Hedgehog signalling pathway and mitigating the ubiquitination of Gli2 in diabetes. In summary, we report a negative regulatory relationship between KIAA0753 and diabetes-related bone loss. The clarification of KIAA0753's role offers valuable insights into the intricate mechanisms underlying diabetic bone complications.

Caring through uncertainty: a qualitative exploration of older colorectal cancer caregivers' experiences during palliative chemotherapy.

PURPOSE: Despite the increasing research on cancer patient caregivers, there is still a lack of detailed understanding about the experiences of spouses caring for elderly colorectal cancer patients. This study aimed to fill this gap by examining the caregiving experiences of spouses during palliative chemotherapy for elderly Chinese colorectal cancer patients. METHODS: Using a qualitative descriptive design, we recruited spousal caregivers of elderly colorectal cancer patients undergoing palliative chemotherapy. Semistructured interviews were conducted, and thematic analysis was employed to analyse the data. RESULTS: Sixteen caregivers aged 60 to 82 years participated in the interviews. The analysis revealed three main themes: ambivalence, multiple role adaptation to conflicts, and the coexistence of hope and pressure. These themes shed light on the behaviors of older caregivers and the challenges they face, including physical and psychosocial issues associated with aging. CONCLUSION: This study highlights the significant stress and challenges experienced by older caregivers, characterized by intertwined emotions such as anxiety about their spouses' health deterioration, exhaustion from long-term care responsibilities, and anticipation of treatment outcomes.

Adherence with oral nutritional supplements and influencing factors in postoperative patients with digestive tract tumors: a cross-sectional study.

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.

Rational design of Fe, N co-doped porous carbon derived from conjugated microporous polymer as an electrocatalytic platform for oxygen reduction reaction.

Porous iron-nitrogen-doped carbons (FeNC) offer a great platform for construction of cathodic oxygen reduction reaction (ORR) catalysts in fuel cells. However, challenges still remain regarding with the collapse of carbon-skeleton during pyrolysis, uneven distribution of active sites and aggregation of metal atoms. In this work, we synthesized Fe, N co-doped conjugated microporous polymer (FeN-CMP) through a facile bottom-up strategy using 1,3,5-triethynylbenzene and iron-chelated 3,8-dibromo-1,10-phenanthroline as monomers, ensuring the uniform coordination of N with Fe element in network. Then, the resulting FeN-CMP was treated by pyrolysis without structural collapse to obtain porous FeNC electrocatalyst for ORR. The most active catalyst was fabricated under 900 °C, which exhibits remarkable ORR activity in alkaline medium with half-wave potential of 0.796 V (18 mV and 105 mV positive deviation from the commercial Pt/C catalyst and post-doping catalyst), high selectivity with nearly 4e- transfer process and excellent methanol tolerance. Our study first developed porous FeNC electrocatalysts derived from Fe, N-anchoring CMPs based on pre-functionalization of monomers, which exhibits great potential as an alternative to commercial Pt/C catalyst for ORR, and provides a feasible strategy of developing multi-atoms doping catalysts for energy storage and conversion as well as heterogeneous catalysis.

The role and mechanism of SUMO modification in liver disease.

Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease.

Compliance with oral nutritional supplements and its influencing factors in postoperative patients with digestive tract tumors: a cross-sectional study.

BACKGROUND: Oral nutritional supplements are one of the preferred methods of nutritional support for postoperative patients. This study aims to investigate the current status of oral nutritional supplements compliance in postoperative patients with digestive tract tumors and its influencing factors. METHODS: Convenience sampling was employed to select 242 patients who underwent surgery for digestive tract tumors at a tertiary hospital in Shanghai from October 2022 to July 2023 as the study subjects. Data following a normal distribution were analyzed using independent sample t-tests, ANOVA single-factor analysis, Pearson correlation analysis, and multiple linear regression analysis to determine the factors influencing compliance with oral nutritional supplements. RESULTS: A total of 252 questionnaires were distributed, with 10 invalid questionnaires excluded, resulting in an effective questionnaire rate of 96.03%. The compliance score for oral nutritional supplements in postoperative patients with digestive tract tumors was (2.40 ± 1.45), General Self-efficacy Scale (GSES) score was (24.72 ± 4.86), Multidimensional Scale of Perceived Social Support Scale (MSPSS) score was (58.67 ± 11.09), and Belief about Medicines Questionnaire Scale (BMQ) score was (0.17 ± 2.78). Multiple linear regression analysis revealed that age, adverse reactions, educational level, self-efficacy, medication beliefs, and social support were factors influencing compliance with oral nutritional supplements in postoperative patients with digestive tract tumors (P < 0.05). CONCLUSION: Our study revealed that the compliance to oral nutritional supplements among postoperative patients with digestive tract tumors was at a moderate level and was closely associated with age, educational level, adverse reactions to oral nutritional supplements, medication beliefs, social support, and self-efficacy. Nursing staff should conduct nursing assessments based on the specific circumstances of patients and their families, provide personalized health education management plans based on the patients' educational level, enhance patients' nutrition knowledge, improve patient self-efficacy, and enhance social support for patients, while further improving patient nutrition management.

Metabolomic and transcriptomic analysis of the flavonoid biosynthesis pathway in Epimedium sagittatum (Sieb. et Zucc.) Maxim. from distinct locations.

Epimedium sagittatum (Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.

Trends of occupational exposure to ionizing radiation in Central China for the period 2000-2021.

A retrospective analysis of occupational exposure to ionizing radiation from medical uses and industrial uses in the three provinces of Central China from 2000 to 2021 was conducted. The average annual effective dose in medical uses and industrial uses decreased from 2.042 mSv and 2.334 mSv in 2000-2002 to 0.476 mSv and 0.371 mSv in 2021 respectively; the fraction of monitored workers receiving annual dose not exceeding 1 mSv increased from 60.78% and 74.45% in 2000-2002 to 94.20% and 96.85% in 2021 respectively, while receiving annual doses exceeding 20 mSv declined from 1.35% and 1.91% in 2000-2002 to 0.18% and 0.03% in 2021 respectively. The average annual effective dose and NR20 in the period 2000-2021 were relatively high in professional public health institutions (0.955 mSv and 0.004) and hospitals (0.815 mSv and 0.004). In 2021, the average annual effective dose to monitored workers in different occupational categories in medical uses in the three provinces of Central China were in the range of 0.199-0.692 mSv, with interventional radiology received the highest dose and NR20 (0.692 mSv and 0.005); the average annual effective dose ranged from 0.161 to 0.493 mSv in industrial uses, with industrial radiography received the highest dose and NR20 (0.493 mSv and 0.001). Occupational exposure in medical uses and industrial uses declined obviously in Central China, and the groups receiving higher doses are the radiation workers working in hospitals and professional public health institutions, or engaged in interventional radiology, nuclear medicine and industrial radiography, warranting more effective radiation protection measures.

Mitigating nitrogen losses with almost no crop yield penalty during extremely wet years.

Climate change-induced precipitation anomalies during extremely wet years (EWYs) result in substantial nitrogen losses to aquatic ecosystems (Nw). Still, the extent and drivers of these losses, and effective mitigation strategies have remained unclear. By integrating global datasets with well-established crop modeling and machine learning techniques, we reveal notable increases in Nw, ranging from 22 to 56%, during historical EWYs. These pulses are projected to amplify under the SSP126 (SSP370) scenario to 29 to 80% (61 to 120%) due to the projected increases in EWYs and higher nitrogen input. We identify the relative precipitation difference between two consecutive years (diffPr) as the primary driver of extreme Nw. This finding forms the basis of the CLimate Extreme Adaptive Nitrogen Strategy (CLEANS), which scales down nitrogen input adaptively to diffPr, leading to a substantial reduction in extreme Nw with nearly zero yield penalty. Our results have important implications for global environmental sustainability and while safeguarding food security.

A salt-concentrated electrolyte for aqueous ammonium-ion hybrid batteries.

The development of aqueous ammonium-ion batteries (AAIBs) is currently attracting great attention because of the interesting electrochemical features induced by the charge carrier NH4+. One possible way to improve the performance of AAIBs is increasing the salt concentration in the electrolyte. Yet, few studies focus on the complex electrode-electrolyte interface behaviors in highly concentrated electrolytes, which affect the electrochemical performance of AAIBs significantly. Herein, we aim to understand the impact of CH3COONH4 electrolyte concentration on the NH4+ storage performance of a bimetallic hydroxide material. Experimental and theoretical simulation results indicate that the acetate anion will participate in the construction of the solvated NH4+ in a highly concentrated electrolyte, facilitating the adsorption of the solvated NH4+ cluster on the electrode surface. Besides, a new partial de-solvation model is also proposed, demonstrating an energy favorable de-solvation process. Finally, an ammonium-ion hybrid battery is designed, which provides a high average discharge voltage of 1.7 V and good energy density of 368 W h kg(cathode)-1, outperforming most of the state-of-the-art aqueous batteries. This work provides new understanding about the electrode's interfacial chemistry in different concentrated CH3COONH4 electrolytes, establishes a correlation between the electrolyte concentration and the electrode's performances, and demonstrates the superiority of the hybrid ammonium-ion battery design.

Kaempferol attenuates carbon tetrachloride (CCl4)-induced hepatic fibrosis by promoting ASIC1a degradation and suppression of the ASIC1a-mediated ERS.

BACKGROUND: Kaempferol is a flavonoid derived from the herb, Kaempferia galanga L., in addition to exhibiting a wide range of pharmacological properties, kaempferol is also an anti-inflammatory, anti-lipid metabolizing, and anti-oxidative stress agent. The underlying molecular mechanisms of its effects on vascular endothelial growth factor (VEGF) secretion and activation of hepatic stellate cells (HSCs) are yet unknown. Activated HSCs induces VEGF release and extracellular matrix (ECM) accumulation which are important factors in hepatic fibrosis. PURPOSE: Our aim is to explore how kaempferol may affect hepatic fibrosis and the mechanisms behind its effects. METHODS: The in vivo model was Sprague-Dawley rats induced with carbon tetrachloride (CCl4). Histological staining was used to observe histological features of the liver. The levels of (alanine aminotransferase) ALT and (aspartate aminotransferase) AST were detected by the corresponding kits. Platelet-derived growth factor (PDGF) was used to stimulate the HSC-T6 rat hepatic stellate cells. The mechanisms underlying this process were investigated using a variety of molecular approaches, including immunofluorescence, RT-qPCR, and western blotting. Moreover, intracellular Ca2+ were observed by laser confocal microscope. RESULTS: It was found that kaempferol significantly reduced the expression of ASIC1a, VEGF, α-SMA and Collagen-I proteins in a model of CCl4-induced hepatic fibrosis in rats. In HSC-T6, kaempferol inhibits activation of HSCs by decreasing expression of ASIC1a, eIF2α, p-eIF2α and ATF-4. Laser confocal fluorescence showed that kaempferol inhibited Ca2+ influx and reduced Ca2+ concentration around the endoplasmic reticulum. Molecular docking and cellular thermal shift assay (CETSA) results further indicated that kaempferol interacted with ASIC1a. We found that kaempferol may promote the degradation of ASIC1a and inhibited ASIC1a- mediated upregulation of ERS. CONCLUSION: The data from our in vivo experiments demonstrate that kaempferol effectively attenuates hepatic fibrosis. In vitro studies we further propose a novel mechanism of kaempferol against hepatic fibrosis which can interact with ASIC1a and promote ASIC1a degradation while inhibiting the activation and VEGF release of HSCs by suppressing the ASIC1a-eIF2α-ATF-4 signaling pathway.

Analysis of HLA Profiles in 390 Uveitis Cases: Insights into Clinical Presentations.

Objective: This study aimed to explain the associations between different types of uveitis and human leukocyte antigen (HLA)-B27, HLA-DR4, and HLA-DRw53. Methods: A retrospective analysis of 390 uveitis cases was conducted among inpatients and outpatients diagnosed at Weifang Eye Hospital from 2013 to 2016. All 390 patients underwent HLA-B27 examination, and an additional 40 patients underwent examination for HLA-DR4 and HLA-DRw53. Gender, age, corrected visual acuity (CVA), and recurrence frequency were statistically analyzed based on the onset site and etiology classification. Results: Among the 390 enrolled patients, 206 were male, and 183 were female, with ages ranging from 6 to 87 years (mean: 44.2). The disease onset was classified into anterior uveitis (AU), panuveitis (panU), posterior uveitis (PU), and intermediate uveitis in 180, 112, 88, and 10 cases, respectively. HLA-B27 was positive in 94 cases (53 males and 41 females), yielding a positive rate of 24.1%. In AU patients, 80 (44.4%) tested positive for HLA-B27, while 8 (7.1%) panU patients and 6 PU patients (6.8%) were HLA-B27 positive; none of the intermediate uveitis (IU) patients exhibited HLA-B27 positivity. HLA-B27, HLA-DR4, and HLA-DRw53 examinations were performed on 40 patients with binocular uveitis, resulting in 2 HLA-B27 positive cases, 15 HLA-DR4 positive cases, and 20 HLA-DRw53 positive cases, with positive rates of 5%, 37.5%, and 50%, respectively. Among 25 Vogt Koyanagi-Harada (VKH) cases, 1 tested positive for HLA-B27, 22 were positive for HLA-DR4, and 24 were positive for HLA-DRw53, with positive rates of 4%, 88%, and 96%, respectively. No positive HLA-B27, HLA-DR4, or HLA-DRw53 cases were found among the 10 cases of Behcet's disease (BD). Conclusions: Human leukocyte antigens (HLAs) play a significant role in the mechanism of uveitis. HLA-B27 exhibits high diagnostic value in acute AU, while HLA-DR4 and HLA-DRw53 are crucial for diagnosing binocular uveitis, particularly Vogt Koyanagi-Harada (VKH) syndrome. Further investigation is warranted to explore the relationship between HLA-DR4, HLA-DRw53, and uveitis.

Recent advances in ß-cyclodextrin-based materials for chiral recognition.

In nature, enantiomers are pairs of chiral compounds, and have semblable chemical and physical properties but mostly show opposite biological effects when they enter an organism. Therefore, chiral recognition has a crucial research value in the fields of medicine, food, biochemistry, etc. Cyclodextrins (CDs) are produced by cyclodextrin glucosyltransferase in some species of bacillus on starch and include three main members α-, ß-, and γ-CD with six, seven and eight units of glucose, respectively. With a hydrophilic external cavity and a hydrophobic internal cavity, ß-CD can also combine with a variety of materials (e.g., graphene, nanoparticles, COFs, and OFETs) to enhance the chiral recognition of guest molecules in a chiral sensor. This review presents the progress of ß-CD modification with different materials for chiral recognition and describes in detail how different materials assist ß-CD in chiral recognition and improve the effect of ß-CD chiral discrimination.

Precolumn derivatization LC-MS/MS method to simultaneous quantitation of 10 monosaccharides in rat plasma.

Monosaccharides are essential for maintaining the normal physiological functions of living organisms. Under disease states, metabolic disorders in vivo will inevitably affect the levels of monosaccharides, which brings the possibility of monosaccharides as a biomarker of some diseases. In this study, a method was developed and validated for simultaneously determining 10 monosaccharides (glucose, galactose, mannose, rhamnose, fucose, xylose, iduronic acid, glucuronic acid, N-acetylgalactosamine and N-acetylglucosamine) in SD rat plasma using liquid chromatography-tandem mass spectrometry. The method employed 1-phenyl-3-methyl-5-pyrazolone (PMP) as a derivatization reagent, considerably improved the chromatographic retention and ionization efficiency of monosaccharides. After protein precipitation of plasma samples, monosaccharides and isotope internal standards were derivatized and liquid-liquid extraction was performed to remove excess PMP. To achieve the baseline separation of several isomers, the resulting derivatives were chromatographed on a Bridged ethyl hybrid (BEH) Phenyl column using gradient elution with a total run time of 8 min. The method was linear within the range of 0.0100-5.00 µg/mL for rhamnose, 0.0500-25.0 µg/mL for fucose, xylose, iduronic acid, glucuronic acid, N-acetylgalactosamine and N-acetylglucosamine, 1.00-500 µg/mL for galactose, 10.0-5000 µg/mL for mannose, and 50.0-25,000 µg/mL for glucose. And the accuracy and precision verification of surrogate matrix samples and plasma samples met the required criteria. The method has been used successfully to study the effect of hepatic insufficiency on monosaccharide levels in rats. It was found that the concentration of glucuronic acid in SD rat plasma was abnormally increased in rats with liver injury.

A Novel Multicellular Placental Barrier Model to Investigate the Effect of Maternal Aflatoxin B1 Exposure on Fetal-Side Neural Stem Cells.

Ingestion of food toxins such as aflatoxin B1 (AFB1) during pregnancy may impair fetal neurodevelopment. However, animal model results may not be accurate due to the species' differences, and testing on humans is ethically impermissible. Here, we developed an in vitro human maternal-fetal multicellular model composed of a human hepatic compartment, a bilayer placental barrier, and a human fetal central nervous system compartment using neural stem cells (NSCs) to investigate the effect of AFB1 on fetal-side NSCs. AFB1 passed through the HepG2 hepatocellular carcinoma cells to mimic the maternal metabolic effects. Importantly, even at the limited concentration (0.0641 ± 0.0046 µM) of AFB1, close to the national safety level standard of China (GB-2761-2011), the mixture of AFB1 crossing the placental barrier induced NSC apoptosis. The level of reactive oxygen species in NSCs was significantly elevated and the cell membrane was damaged, causing the release of intracellular lactate dehydrogenase (p < 0.05). The comet experiment and γ-H2AX immunofluorescence assay showed that AFB1 caused significant DNA damage to NSCs (p < 0.05). This study provided a new model for the toxicological evaluation of the effect of food mycotoxin exposure during pregnancy on fetal neurodevelopment.

Walnut polyphenols and the active metabolite urolithin A improve oxidative damage in SH-SY5Y cells by up-regulating PKA/CREB/BDNF signaling.

Accumulating evidence has confirmed the health benefits of walnut diets in maintaining brain function with age. Recent studies have indicated that walnut polyphenols (WP) and their active metabolites urolithins may play an important role in the health benefits of walnut diets. In the present study, we evaluated the protective effect of WP and urolithin A (UroA) on H2O2-induced damage in human neuroblastoma (SH-SY5Y) cells, and investigated its mechanisms in the cAMP-response element binding protein (CREB)-mediated signaling pathway, which is tightly involved in neurodegenerative and neurological diseases. The results demonstrated that both WP (50 and 100 µg mL-1) and UroA (5 and 10 µM) treatment significantly reversed the decrease of cell viability, the leakage of extracellular lactate dehydrogenase (LDH), the overload of intracellular calcium and cell apoptosis induced by H2O2 treatment. Moreover, WP and UroA treatment also relieved H2O2-induced oxidative stress including overproduction of intracellular reactive oxygen species (ROS) and reduced activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, western blot analysis showed that WP and UroA treatment significantly increased the activity of cAMP-dependent protein kinase A (PKA) and the expression of pCREB (Ser133) and its downstream molecule brain-derived neurotrophic factor (BDNF), which were decreased by H2O2 treatment. Furthermore, pretreatment with the PKA inhibitor H89 abolished the protective effects of WP and UroA, indicating that up-regulation of the PKA/CREB/BDNF neurotrophic signaling pathway is required for their neuroprotective effects against oxidative stress. The current work provides new perspectives for understanding the beneficial effects of WP and UroA on brain function, which warrants further investigation.

Solid state ionics enabled ultra-sensitive detection of thermal trace with 0.001K resolution in deep sea.

The deep sea remains the largest uncharted territory on Earth because it's eternally dark under high pressure and the saltwater is corrosive and conductive. The harsh environment poses great difficulties for the durability of the sensing method and the device. Sea creatures like sharks adopt an elegant way to detect objects by the tiny temperature differences in the seawater medium using their extremely thermo-sensitive thermoelectric sensory organ on the nose. Inspired by shark noses, we designed and developed an elastic, self-healable and extremely sensitive thermal sensor which can identify a temperature difference as low as 0.01 K with a resolution of 0.001 K. The sensor can work reliably in seawater or under a pressure of 110 MPa without any encapsulation. Using the integrated temperature sensor arrays, we have constructed a model of an effective deep water mapping and detection device.