An Anthocyanin-Based Eco-Friendly Triboelectric Nanogenerator for pH Monitoring and Energy Harvesting.

In recent years, renewable and sustainable triboelectric nanogenerators have attracted attention due to their high energy conversion rate, and enhancing their functionality further contributes to their applicability across various fields. A pH-sensitive triboelectric nanogenerator (pH-TENG) has been prepared by electrostatic spinning technology, with anthocyanin as the pH indicator and environmentally friendly polyvinyl alcohol (PVA) as the substrate. Among many friction-negative materials, the pH-TENG exhibits the best combination with fluorinated ethylene propylene (FEP) and yields an open-circuit voltage of 62 V, a short-circuit current of 370 nA, and a transferred charge of 21.8 nC. At a frequency of 3 Hz, it can charge a 4.7 µF capacitor to 2 V within 45 s, effectively powering a thermometer. Furthermore, the presence of anthocyanin does not affect the pH-TENG's power generation performance and enables the monitoring of a wide range of environmental pH changes, with an ΔE change of 28.8 ± 7.6. Therefore, pH-TENG prepared with environmentally friendly materials can bring new available materials to the biological and medical fields.

New Carbon Materials for Multifunctional Soft Electronics.

Soft electronics are garnering significant attention due to their wide-ranging applications in artificial skin, health monitoring, human-machine interaction, artificial intelligence, and the Internet of Things. Various soft physical sensors such as mechanical sensors, temperature sensors, and humidity sensors are the fundamental building blocks for soft electronics. While the fast growth and widespread utilization of electronic devices have elevated life quality, the consequential electromagnetic interference (EMI) and radiation pose potential threats to device precision and human health. Another substantial concern pertains to overheating issues that occur during prolonged operation. Therefore, the design of multifunctional soft electronics exhibiting excellent capabilities in sensing, EMI shielding, and thermal management is of paramount importance. Because of the prominent advantages in chemical stability, electrical and thermal conductivity, and easy functionalization, new carbon materials including carbon nanotubes, graphene and its derivatives, graphdiyne, and sustainable natural-biomass-derived carbon are particularly promising candidates for multifunctional soft electronics. This review summarizes the latest advancements in multifunctional soft electronics based on new carbon materials across a range of performance aspects, mainly focusing on the structure or composite design, and fabrication method on the physical signals monitoring, EMI shielding, and thermal management. Furthermore, the device integration strategies and corresponding intriguing applications are highlighted. Finally, this review presents prospects aimed at overcoming current barriers and advancing the development of state-of-the-art multifunctional soft electronics.

Multistrand Twisted Triboelectric Kevlar Yarns for Harvesting High Impact Energy, Body Injury Location and Levels Evaluation.

Developing ultrahigh-strength fabric-based triboelectric nanogenerators for harvesting high-impact energy and sensing biomechanical signals is still a great challenge. Here, the constraints are addressed by design of a multistrand twisted triboelectric Kevlar (MTTK) yarn using conductive and non-conductive Kevlar fibers. Manufactured using a multistrand twisting process, the MTTK yarn offers superior tensile strength (372 MPa), compared to current triboelectric yarns. In addition, a self-powered impact sensing fabric patch (SP-ISFP) comprising signal acquisition, processing, communication circuit, and MTTK yarns is integrated. The SP-ISFP features withstanding impact (4 GPa) and a sensitivity and response time under the high impact condition (59.68 V GPa-1 ; 0.4 s). Furthermore, a multi-channel smart bulletproof vest is developed by the array of 36 SP-ISFPs, enabling the reconstruction of impact mapping and assessment of body injury location and levels by real-time data acquisition. Their potential to reduce body injuries, professional security, and construct a multi-point personal vital signs dynamic monitoring platform holds great promise.

Effectiveness of a broad-spectrum bivalent mRNA vaccine against SARS-CoV-2 variants in preclinical studies.

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.

Sufficient driving force for quinoidal isoindigo-based diradicaloids with tunable diradical characters.

Stable organic π-conjugated diradcialoids with tunable diradical characters can profoundly affect emerging technology. Over the past years, great efforts have been devoted to studying the structure-diradical character relationship in diradicaloids. Herein, a series of quinoidal isoindigo (IID) compounds with different attached terminal end groups were designed. Detailed analysis focuses on elucidating the driving force for evoking and enhancing the diradical character in the quinoidal IID systems. The arylene units of the IID core and the bridged aromatic units determine the contribution of the open-shell diradical form in the ground state. Diradical character y0 correlates well with bond length alternation (BLA), the total HOMA, and the total NICS(1)zz, and it is tuned by bridged aromatic units and terminal end groups in symmetric systems. The zwitterionic character weakens the diradical character in asymmetric systems to different extents. This work contributes to the deep understanding of evoking and enhancing the diradical character in quinoidal IID-based diradcialoids, providing useful guidelines to produce new molecules with desirable properties.

Pentachloronitrobenzene disturbed murine ventricular wall development by inhibiting cardiomyocyte proliferation via Hec1 downregulation.

Exposure to the organochlorine fungicide pentachloronitrobenzene (PCNB) causes developmental abnormalities, including cardiac malformation. However, the molecular mechanism of PCNB cardiotoxicity remains elusive. We found that oral administration of PCNB to pregnant mice induced a hypoplastic wall with significant thinning of the compact myocardium in the developing hearts. PCNB significantly downregulates the expression of Hec1, a member of the NDC80 kinetochore complex, resulting in aberrant spindles, chromosome missegregation and an arrest in cardiomyocyte proliferation. Cardiac-specific ablation of Hec1 sharply inhibits cardiomyocyte proliferation, leading to thinning of the compact myocardium and embryonic lethality. Mechanistically, we found that activating transcription factor 3 (ATF3) transactivates Hec1 expression. Either HEC1 or ATF3 overexpression significantly rescues mitotic defects and restore the decreased proliferative ability of cardiomyocytes caused by PCNB exposure. Our findings highlight that maternal PCNB exposure disrupts embryonic cardiac function by inhibiting cardiomyocyte proliferation and interfering with ventricular wall development, partially attributed to the downregulation of the Atf3-Hec1 axis.

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants.

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants.

α-Linolenic acid-regulated testosterone biosynthesis via activation of the JNK-SF-1 signaling pathway in primary rooster Leydig cells.

As a functional fatty acid, α-linolenic acid (ALA) is essential in promoting animal testosterone biosynthesis. This study investigated the effects of ALA on testosterone biosynthesis and the possible mechanism underlying the signaling pathway in primary Leydig cells of the rooster. METHODS: Primary rooster Leydig cells were treated with ALA (0, 20, 40, or 80 µmol/L) or pretreated with a p38 inhibitor (50 µmol/L), a c-Jun NH2-terminal kinase (JNK) inhibitor (20 µmol/L), or an extracellular signal-regulated kinase (ERK) inhibitor (20 µmol/L) before ALA treatment. Testosterone content in the conditioned culture medium was detected using an enzyme-linked immunosorbent assay (ELISA). The expression of steroidogenic enzymes and JNK-SF-1 signaling pathway factors was detected using real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Supplementation with ALA significantly increased testosterone secretion within culture media (P < 0.05), and the optimized dose was 40 µmol/L. Compared with the control group, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA expression significantly increased (P < 0.05) in the 40 µmol/L ALA group; 17-hydroxylase/c17-20 lyase (P450c17) and p38 mRNA expressions were not significantly different in the 40 µmol/L ALA group; ERK and JNK mRNA expressions were significantly upregulated (P < 0.05) in 40 µmol/L ALA group. In the inhibitor group, testosterone levels were significantly downregulated (P < 0.05). Compared with the 40 µmol/L ALA group, StAR, P450scc, and P450c17 mRNA expressions were significantly decreased (P < 0.05), and 3ß-HSD mRNA expression in the p38 inhibitor group did not change; StAR, P450scc, and 3ß-HSD mRNA expressions were significantly decreased (P < 0.05), and P450c17 mRNA expression in ERK inhibitor group did not change; StAR, P450scc, 3ß-HSD, and P450c17 mRNA expressions were significantly decreased (P < 0.05) in JNK inhibitor group. Additionally, the increased steroidogenic factor 1 (SF-1) gene expression levels induced by ALA were reversed when the cells were pre-incubated with JNK and ERK inhibitors. The levels in the JNK inhibitor group were significantly lower than those in the control group (P < 0.05). CONCLUSION: ALA may promote testosterone biosynthesis by activating the JNK-SF-1 signaling pathway to upregulate StAR, P450scc, 3ß-HSD, and P450c17 expression in primary rooster Leydig cells.

Driving mechanism of water replenishment on DOM composition and eutrophic status changes of lake in arid and semi-arid regions of loess area.

Water replenishment can be a key factor in driving lake eutrophication status. In arid and semi-arid regions of China, water replenishment for a lake has been widely carried out for not only improving water environmental quality, but also maintaining ecological system function. However, it is still unclear in terms of mechanism by which water replenishment drives lake eutrophication status. In this study, fluorescence excitation-emission matrix spectroscopy (EEMs) combined with multiple statistical analysis models (including parallel factor analysis, correlation analysis, redundancy analysis, and partial least squares structural equation modeling) was utilized to reveal potential driving mechanism and causality between water replenishment, dissolved organic matter (DOM) fractions and eutrophic status of Lake Shahu in China. Based on variations of DOM fractions, fulvic-like substances could be accumulated during the replenishment period, while nutrients carried along the replenishment might conduce to increase microbial activities during the non-replenishment period. This should be contributed to an alteration of prominent component from fulvic-like substances to tyrosine-like substances during the replenishment period to non-replenishment period. According to partial least squares structural equation modeling, two potential indirect paths were finally revealed, i.e., water replenishment derived the eutrophic status of Lake Shahu: water replenishment → microbial activity → algae → eutrophication, and water replenishment → microbial activity → eutrophication. This supposed that the water replenishment should indirectly drive the algae and eutrophication of the lake by promoting the transformation of DOM fractions. In addition, natural conditions could indirectly contribute to the eutrophication of the lake through impacting the algae growth. These findings should be conducive to trace the alteration of DOM fractions in lakes by water replenishment and in recognizing potential driving mechanisms of water replenishment on eutrophication of lakes by changing DOM fractions. This could provide basic theoretical support for policymakers to regulate and treat the eutrophication of lakes.

Recent Advances of Photoactive Near-Infrared Carbon Dots in Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs.

Rab10 protects against DOX-induced cardiotoxicity by alleviating the oxidative stress and apoptosis of cardiomyocytes.

Doxorubicin (DOX) is a widely used anticancer drug, but its clinical application is limited by cardiotoxicity. As a member of the Rab family, Rab10 has multiple subcellular localizations and carries out a wide variety of functions. Here, we explored the role of Rab10 on DOX-induced cardiotoxicity. Cardiac-specific Rab10 transgenic mice were constructed and treated with DOX or saline. We found that cardiac-specific overexpression of Rab10 alleviated cardiac dysfunction and attenuated cytoplasmic vacuolization and mitochondrial damage in DOX-treated mouse heart tissues. Immunofluorescence staining and Western blot analysis showed that Rab10 alleviated DOX-induced apoptosis and oxidative stress in cardiomyocytes in mouse heart tissues. We demonstrated that DOX mediated apoptosis, oxidative stress and depolarization of the mitochondrial membrane potential in H9c2 cells, while overexpression and knockdown of Rab10 attenuated and aggravated these effects, respectively. Furthermore, we found that Mst1, a serine-threonine kinase, was cleaved and translocated into the nucleus in H9c2 cells after DOX treatment, and knockdown of Mst1 alleviated DOX-induced cardiomyocyte apoptosis. Overexpression of Rab10 inhibited the cleavage of Mst1 mediated by DOX treatment in vivo and in vitro. Together, our findings demonstrated that cardiac-specific overexpression of Rab10 alleviated DOX-induced cardiac dysfunction and injury via inhibiting oxidative stress and apoptosis of cardiomyocytes, which may be partially ascribed to the inhibition of Mst1 activity.

Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors.

Strategies to degrade steroid receptors and their alternative splicing isoforms are critical for disease management. Here we report that celastrol recruited the ubiquitin ligase UBE3A and degraded androgen receptor (AR), AR-v7, and glucocorticoid receptor (GR) to suppress prostate cancer development. UBE3A was not an optimal endogenous AR ubiquitin ligase in mice and patients, but celastrol promoted the interaction between UBE3A and AR. Multiple domains of AR, including the DNA binding domain (DBD), were implicated into the UBE3A-AR interaction. Sharing a conserved DBD, GR, AR-v7, and other steroid receptors were recognized and degraded by UBE3A after celastrol treatment. Thus, celastrol suppressed prostate cancer cell proliferation more potently than enzalutamide. Modifying the carboxyl group of celastrol improved its anti-tumor activity. Together, our findings revealed that celastrol might be a potential molecular glue to enhance the interaction between UBE3A and steroid receptors to degrade multiple steroid receptors and splicing isoforms in prostate cancer, paving a way for further drug optimization and disease treatment.

Self-Rebound Cambered Triboelectric Nanogenerator Array for Self-Powered Sensing in Kinematic Analytics.

In challenging and dangerous equestrian sports, kinematic analysis and injury prevention based on distributed, portable, and real-time sensing technology is particularly important. Here, we report a flexible self-rebound cambered triboelectric nanogenerator that addresses the concerns and shows its applications for self-powered sensing in kinematic analysis. Benefiting from simple and effective design, ordinary materials by means of self-rebound cambered structure evolved into a micro-biomechanical energy harvester with mechanical properties including over 3000 cycles durability and superior resiliency and stability. At a size of 4.52 cm2, it could deliver a power density of 1.25 mW/m2 under an external load resistance of 60 MΩ. A self-powered riding characteristic sensing system has been developed with fast response time of 16 ms, to provide real-time statistics data and fall prediction for both horsemen and coaches, to take traditional equestrian sports to a advanced state. This work not only can promote the development of triboelectric nanogenerators in micro-biomechanical energy harvesting, but also could expand the application range of the self-powered system to intelligent sport monitoring and assisting.

Epilepsy-Associated UBE3A Deficiency Downregulates Retinoic Acid Signalling Pathway.

Ubiquitin-protein ligase E3A (UBE3A) has dual functions as a E3 ubiquitin-protein ligase and coactivator of nuclear hormone receptors. Mutations or deletions of the maternally inherited UBE3A gene cause Angelman syndrome. Here, we performed transcriptome profiling in the hippocampus of Ube3a m+/p+ and Ube3a m-/p+ mice, and determined that the expression of the retinoic acid (RA) signalling pathway was downregulated in Ube3a-deficient mice compared to WT mice. Furthermore, we demonstrated that UBE3A directly interacts with RARα and may function as a coactivator of the nuclear receptor RARα to participate in the regulation of gene expression. Loss of UBE3A expression caused the downregulation of the expression of RA-related genes, including Erbb4, Dpysl3, Calb1, Pten, and Arhgap5 in Ube3a m-/p+ mice brain tissues. This work revealed a new role for UBE3A in regulating retinoic acid (RA) signalling downstream genes and hopefully to shed light on the potential drug target of AS.

Arsenic suppresses GDF1 expression via ROS-dependent downregulation of specificity protein 1.

Inorganic arsenic, an environmental contaminant, has adverse health outcomes. Our previous studies showed that arsenic causes abnormal cardiac development in zebrafish embryos by downregulating Dvr1/GDF1 expression and that folic acid protects against these effects. However, the mechanism by which arsenic represses Dvr1/GDF1 expression remains unknown. Herein, we demonstrate that specificity protein 1 (Sp1) acts as a transcriptional activator of GDF1. Arsenic treatment downregulated Sp1 at both the mRNA and protein level and its downstream targets GDF1 and SIRT1. Chromatin immunoprecipitation analysis showed that the occupancy of Sp1 on the GDF1 or SIRT1 promoter was significantly reduced in response to arsenite. Further investigation showed that Sp1 overexpression inhibited the arsenic-mediated decrease in GDF1 and SIRT1, while Sp1 knockdown had the opposite effect. We found that expression of the oxidative adaptor p66shc was inversely related to that of SIRT1 and that the binding of SIRT1 to the p66shc promoter was sharply attenuated by arsenite treatment. SIRT1 overexpression attenuated p66shc expression but enhanced GDF1 protein expression, while SIRT1 depletion exerted the opposite effect. Both the antioxidants N-acetylcysteine and folic acid reversed the arsenic-mediated repression of Sp1, GDF1 and SIRT1. Moreover, wild-type p66shc overexpression enhanced the arsenic-mediated repression of Sp1, GDF1 and SIRT1, which was accompanied by an increase in intracellular reactive oxygen species (ROS) levels, while both overexpression of a dominant negative p66shcSer36Ala mutant and deficiency in p66shc reversed these effects. Taken together, our results revealed that arsenic suppresses GDF1 expression via the ROS-dependent downregulation of the Sp1/SIRT1 axis, which forms a negative feedback loop with p66shc to regulate oxidative stress. Our findings reveal a novel molecular mechanism underlying arsenic toxicity and provide new insight into the protective effect of folic acid in arsenic-mediated toxicity.

Glycyrrhetinic acid attenuates disturbed vitamin a metabolism in non-alcoholic fatty liver disease through AKR1B10.

Abnormal vitamin A (retinol) metabolism plays an important role in the occurrence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this study, NAFLD and NASH models were established to investigate the effects of food additives glycyrrhizic acid (GL) on retinol metabolism in NAFLD/NASH mice. Potential targets of GL and its active metabolite glycyrrhetinic acid (GA) were analyzed by RNA sequence, bioinformatics, and molecular docking analyses. Gene transfection and enzymatic kinetics were used to identify the target of GL. The results showed that GL could resolve the fatty and inflammatory lesions in the mouse liver, thereby improving the disorder of retinol metabolism. RNA sequence analysis of model mice liver revealed significant changes in AKR1B10 (retinol metabolic enzymes). Bioinformatics and molecular docking analyses showed that AKR1B10 is a potential target of GA but not GL. GA could inhibit AKR1B10 activity, which then affects retinol metabolism, whereas GL only had the same effect after hydrolysis into GA. In AKR1B10-KO hepatocytes, GA, GL, and hydrolysates of GL had no regulatory effect on retinol metabolism. Therefore, GA, the active metabolite of GL, as a novel AKR1B10 inhibitor, could promote retinoic acid synthesis. GL restored the balance of retinol metabolism in NAFLD/NASH mice by metabolizing to GA.

Publisher Correction: The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Open Reduction Effects of Digitally Treating Zygomaticomaxillary Complex Fractures With Bio-Resorbable Materials.

PURPOSE: The application of bio-resorbable plates in craniomaxillofacial surgery is increasing because of the advantage of avoiding secondary surgery. This study aimed to evaluate the effects of osteosynthesis with prebent bio-resorbable plates for treating zygomaticomaxillary complex (ZMC) fractures. MATERIALS AND METHODS: We implemented a prospective case series composed of patients with ZMC fractures who underwent treatment at the School of Stomatology at China Medical University. Bio-resorbable plates were used for fracture fixation. The fractures were stabilized with bio-resorbable plates prebent on a 3-dimensionally printed skull model with the fractures reduced using virtual simulation. The primary outcome variable was the stability rate of reduced bone segments. Other study variables were mouth opening, occlusion, paresthesia or anesthesia in the infraorbital nerve region (PAIN), and diplopia. Outcome variables were determined by calculating stability rates of reduced bone segments, resolution rates of postoperative restricted mouth opening, malocclusion, PAIN, and diplopia. RESULTS: The sample was composed of 11 patients recruited between November 2016 and September 2018. All surgical procedures were successful, with no severe complications. The stability rate of reduced bone segments from different mechanical buttress regions was 100%. Satisfactory postoperative stability of bio-resorbable plates was obtained in all cases. The resolution rates of postoperative restricted mouth opening and malocclusion were 75 and 100%, respectively. PAIN and diplopia symptoms resolved in 50 and 100% of cases, respectively. CONCLUSIONS: The results suggest that osteosynthesis with bio-resorbable plates prebent on a 3-dimensionally printed skull model, designed by virtual simulation, works well for patients with ZMC fractures. Future studies should focus on the broader applications of these findings in the practice of oral and maxillofacial surgery.

Establishment and application of a 10-plex liquid bead array for the simultaneous rapid detection of animal species.

BACKGROUND: Meat fraud and adulteration incidents occur frequently in almost all regions of the globe, especially with the increase in the world's population. To ensure the authenticity of meat products, we developed a 10-plex xMAP assay to simultaneously detect ten animal materials: bovine, caprine, poultry, swine, donkey, deer, horse, dog, fox and mink. RESULTS: This method was investigated by analyzing DNA extracts from raw muscle, muscle mixtures, meat products and animal feeds. Our results indicated that the species of interest can be identified, differentiated and detected down to 1 g kg-1 in binary mixtures or 0.01-0.001 ng of genomic DNA from specific species. Testing of 125 commercial samples showed a 97.4% coincidence rate with the method used in routine testing in our lab. CONCLUSION: These results indicated that the method established in this study could detect ten animal materials simultaneously within 3 h, which provides a new, useful tool for animal ingredient analysis in meat products and animal feeds. © 2019 Society of Chemical Industry.

Pentachloronitrobenzene alters progesterone production and primordial follicle recruitment in cultured granulosa cells and rat ovary†.

Pentachloronitrobenzene (PCNB) is an organochlorine fungicide widely used for crop production and has become an environmental concern. Little is known about the effect of PCNB on ovarian steroidogenesis and follicular development. We found that PCNB stimulated Star expression and progesterone production in cultured rat granulosa cells in a dose-dependent manner. PCNB activated mitogen-activated protein kinase (MAPK3/1) extracellulat regulated kinase (ERK1/2), thus inhibition of either protein kinase A (PKA) or MAPK3/1 signaling pathway significantly attenuated progesterone biosynthesis caused by PCNB, suggesting that PCNB induced progesterone production by activating the cyclic adenosine monophosphate (cAMP/PKA) and MAPK3/1 signaling pathways. Further investigation demonstrated that PCNB induced Star expression and altered MAPK3/1 signaling in ovary tissues of immature SD rats treated with PCNB at the dose of 100, 200, or 300 mg/kg by daily gavage for 7 days, while serum progesterone level was dose-dependently decreased. We demonstrated that PCNB exposure accelerated the recruitment of primordial follicles into the growing follicle pool in ovary tissues, accompanied by increased levels of anti-Mullerian hormone (AMH) in both ovary tissues and serum. Taken together, our data demonstrate for the first time that PCNB stimulated Star expression, altered MAPK3/1 signaling and progesterone production in vivo and in vitro, and accelerated follicular development with a concomitant increase in AMH in ovary tissues and serum. Our findings provide novel insight into the toxicity of PCNB to animal ovary function.