Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring.

Stress during pregnancy is often linked with increased incidents of neurodevelopmental disorders, including cognitive impairment. Here, we report that stress during pregnancy leads to alterations in the intestinal flora, which negatively affects the cognitive function of offspring. Cognitive impairment in stressed offspring can be reproduced by transplantation of cecal contents of stressed pregnant rats (ST) to normal pregnant rats. In addition, gut microbial dysbiosis results in an increase of ß-guanidinopropionic acid in the blood, which leads to an activation of the adenosine monophosphate-activated protein kinase (AMPK) and signal transducer and activator of transcription 3 (STAT3) in the fetal brain. Moreover, ß-guanidinopropionic acid supplementation in pregnant rats can reproduce pregnancy stress-induced enhanced glial differentiation of the fetal brain, resulting in impaired neural development. Using probiotics to reconstruct maternal microbiota can correct the cognitive impairment in the offspring of pregnant stressed rats. These findings suggest that microbial reconstitution reverses gestational stress-induced cognitive impairment and synaptic deficits in male rat offspring.

A quadratic isothermal amplification fluorescent biosensor without intermediate purification for ultrasensitive detection of circulating tumor DNA.

Circulating tumor DNA (ctDNA) is an auspicious tumor biomarker released into the bloodstream by tumor cells, offering abundant information concerning cancer genes. It plays a crucial role in the early diagnosis of cancer. However, due to extremely low levels in body fluids, achieving a simple, sensitive, and highly specific detection of ctDNA remains challenging. Here, we constructed a purification-free fluorescence biosensor based on quadratic amplification of ctDNA by combining nicking enzyme mediated amplification (NEMA) and catalytic hairpin assembly (CHA) reactions. After double isothermal amplification, this biosensor achieved an impressive signal amplification of nearly 107-fold, enabling it to detect ctDNA with ultra-sensitivity. And the detection limit of this biosensor is as low as 2 aM. In addition, we explored the influence of human serum on the performance of the biosensor and found that it showed favorable sensitivity in the presence of serum. This biosensor eliminates the need for an intermediate purification step, resulting in enhanced sensitivity and convenience. Thus, our purification-free fluorescent biosensor exhibits ultra-high sensitivity when compared to other biosensors and has the potential to serve as an effective diagnostic tool for early detection of cancer.

A label-free colorimetric biosensor utilizing natural material for highly sensitive exosome detection.

Exosomes, extracellular vesicles secreted by cells, play a crucial role in intercellular communication by transferring information from source cells to recipient cells. These vesicles carry important biomarkers, including nucleic acids and proteins, which provide valuable insights into the parent cells' status. As a result, exosomes have emerged as noninvasive indicators for the early diagnosis of cancer. Colorimetric biosensors have garnered significant attention due to their cost-effectiveness, simplicity, rapid response, and reproducibility. In this study, we employ sporopollenin microcapsules (SP), a natural biopolymer material derived from pollen, as a substrate for gold nanoparticles (AuNPs). By modifying the SP-Au complex with CD63 aptamers, we develop a label-free colorimetric biosensor for exosome detection. In the absence of exosomes, the SP-Au complex catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), resulting in a color change from colorless to blue. However, the addition of exosomes inhibits the catalytic activity of the SP-Au complex due to coverage of exosomes on AuNPs. This colorimetric biosensor exhibits high sensitivity and selectivity for exosome detection, with a detection limit of 10 particles/µL and a wide linear range of 10 - 108 particles/µL. Additionally, the SP-Au biosensor demonstrates remarkable resistance to serum protein adsorption and excellent catalytic stability even in harsh environments, making it highly suitable for clinical diagnostics.

Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats.

The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning.

SIRT3-Mediated Deacetylation of SDHA Rescues Mitochondrial Bioenergetics Contributing to Neuroprotection in Rotenone-Induced PD Models.

Mitochondrial dysfunction is critically involved in the degeneration of dopamine (DA) neurons in the substantia nigra, a common pathological feature of Parkinson's disease (PD). Previous studies have demonstrated that the NAD+-dependent acetylase Sirtuin 3 (SIRT3) participates in maintaining mitochondrial function and is downregulated in aging-related neurodegenerative disorders. The exact mechanism of action of SIRT3 on mitochondrial bioenergetics in PD pathogenesis, however, has not been fully described. In this study, we investigated the regulatory role of SIRT3-mediated deacetylation of mitochondrial complex II (succinate dehydrogenase) subunit A (SDHA) and its effect on neuronal cell survival in rotenone (ROT)-induced rat and differentiated MN9D cell models. The results revealed that SIRT3 activity was suppressed in both in vivo and in vitro PD models. Accompanying this downregulation of SIRT3 was the hyperacetylation of SDHA, impaired activity of mitochondrial complex II, and decreased ATP production. It was found that the inhibition of SIRT3 activity was attributed to a reduction in the NAD+/NADH ratio caused by ROT-induced inhibition of mitochondrial complex I. Activation of SIRT3 by icariin and honokiol inhibited SDHA hyperacetylation and increased complex II activity, leading to increased ATP production and protection against ROT-induced neuronal damage. Furthermore, overexpression of SDHA also exerted potent protective benefits in cells treated with ROT. In addition, treatment of MN9D cells with the NAD+ precursor nicotinamide mononucleotide increased SIRT3 activity and complex II activity and promoted the survival of cells exposed to ROT. These findings unravel a regulatory SIRT3-SDHA axis, which may be closely related to PD pathology. Bioenergetic rescue through SIRT3 activation-dependent improvement of mitochondrial complex II activity may provide an effective strategy for protection from neurodegeneration.

Variational Entanglement-Assisted Quantum Process Tomography with Arbitrary Ancillary Qubits.

Quantum process tomography is a pivotal technique in fully characterizing quantum dynamics. However, exponential scaling of the Hilbert space with the increasing system size extremely restrains its experimental implementations. Here, we put forward a more efficient, flexible, and error-mitigated method: variational entanglement-assisted quantum process tomography with arbitrary ancillary qubits. Numerically, we simulate up to eight-qubit quantum processes and show that this tomography with m ancillary qubits (0≤m≤n) alleviates the exponential costs on state preparation (from 4^{n} to 2^{n-m}), measurement settings (at least a 1 order of magnitude reduction), and data postprocessing (efficient and robust parameter optimization). Experimentally, we first demonstrate our method on a silicon photonic chip by rebuilding randomly generated one-qubit and two-qubit unitary quantum processes. Further using the error mitigation method, two-qubit quantum processes can be rebuilt with average gate fidelity enhanced from 92.38% to 95.56%. Our Letter provides an efficient and practical approach to process tomography on the noisy quantum computing platforms.

The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment.

The tumor microenvironment (TME) is related to chronic inflammation and is currently identified as a risk factor for the occurrence and development of endometrial cancer (EC). Pyroptosis is a new proinflammatory form of programmed cell death that plays a critical role in the progression of multiple diseases. However, the important role of pyroptosis in high-glucose (HG)-related EC and the underlying molecular mechanisms remain elusive. In the present study, transcriptome high-throughput sequencing revealed significantly higher hexokinase domain-containing 1 (HKDC1) expression in EC patients with diabetes than in EC patients with normal glucose. Mechanistically, HKDC1 regulates HG-induced cell pyroptosis by modulating the production of reactive oxygen species and pyroptosis-induced cytokine release in EC. In addition, HKDC1 regulates TME formation by enhancing glycolysis, promoting a metabolic advantage in lactate-rich environments to further accelerate EC progression. Subsequently, miR-876-5p was predicted to target the HKDC1 mRNA, and HOXC-AS2 was identified to potentially inhibit the miR-876-5p/HKDC1 axis in regulating cell pyroptosis in HG-related EC. Collectively, we elucidated the regulatory role of the HOXC-AS2/miR-876-5p/HKDC1 signal transduction axis in EC cell pyroptosis at the molecular level, which may provide an effective therapeutic target for patients with diabetes who are diagnosed with EC.

[Stem photosynthesis and its main influencing factors of Haloxylon ammodendron and Tamarix ramosissima.] / æ¢­æ¢­å’Œå¤šæžæŸ½æŸ³çš„æžå¹²å ‰åˆåŠå ¶ä¸»è¦å½±å“å› å­.

Stem photosynthesis (Pg) is an alternative and significant carbon source, playing a crucial role in plant survival under extreme environment. The main aims of this study were to quantify stem and leaf photosynthesis, find out the main drivers of Pg, and estimate the contributions of Pg to plant individual carbon balance of two dominant species Haloxylon ammodendron and Tamarix ramosissima in Gurbantunggut Desert. A Li-Cor 6400 portable photosynthesis system and a special chamber were used to measure leaf and stem photosynthesis. Ancillary measurements included leaf/stem functional trait (chlorophyll content, water content, leaf/stem area, carbon/nitrogen content, etc.) and environmental factors (air temperature and humidity, photosynthetically active radiation, soil temperature, and soil water content). Our results showed that Pg of H. ammodendron and T. ramosissima was 2.37 and 0.98 µmol·m-2·s-1, Pg refixation CO2 of stem respiration by 65%-76% and 57%-77% in H. ammodendron and T. ramosissima. Pg was influenced by photosynthetically active radiation, air temperature, soil temperature and water vapor deficit. Pg assimilation CO2 accounted for 8.2%-16.6% and 3.6%-8.3% of CO2 assimilation of H. ammodendron and T. ramosissima, respectively. The maximum value appeared at noon when temperature was high. There might be fundamental defects if we ignore the contribution of branch photosynthesis when predicting carbon process of desert ecosystem under the background of climate change.

Epidemic spreading with migration in networked metapopulation.

Migration plays a crucial role in epidemic spreading, and its dynamic can be studied by metapopulation model. Instead of the uniform mixing hypothesis, we adopt networked metapopulation to build the model of the epidemic spreading and the individuals' migration. In these populations, individuals are connected by contact network and populations are coupled by individuals migration. With the network mean-field and the gravity law of migration, we establish the N-seat intertwined SIR model and obtain its basic reproduction number ℛ 0 . Meanwhile, we devise a non-markov Node-Search algorithm for model statistical simulations. Through the static network migration ansatz and ℛ 0 formula, we discover that migration will not directly increase the epidemic replication capacity. But when ℛ 0 > 1 , the migration will make the susceptive population evolve from metastable state (disease-free equilibrium) to stable state (endemic equilibrium), and then increase the influence area of epidemic. Re-evoluting the epidemic outbreak in Wuhan, top 94 cities empirical data validate the above mechanism. In addition, we estimate that the positive anti-epidemic measures taken by the Chinese government may have reduced 4 million cases at least during the first wave of COVID-19, which means those measures, such as the epidemiological investigation, nucleic acid detection in medium-high risk areas and isolation of confirmed cases, also play a significant role in preventing epidemic spreading after travel restriction between cities.

Amplification of anticancer efficacy by co-delivery of doxorubicin and lonidamine with extracellular vesicles.

Chemotherapy is commonly used for the treatment of lung cancer, but strong side effects and low treatment efficacy limit its clinical application. Here, extracellular vesicles (EVs) as natural drug delivery carriers were used to load conventional anticancer drug doxorubicin (DOX) and a chemosensitizer lonidamine (LND). Two types of EVs with different sizes (16k EVs and 120k EVs) were prepared using different centrifugation forces. We found that co-delivery of DOX and LND with both EVs enhanced the cytotoxicity and reduced the dose of the anticancer drug significantly in vitro. Effective delivery of anti-cancer drugs to cancer cells was achieved by direct fusion of EVs with the plasma membrane of cancer cells. On the other hand, DOX and LND inhibited cancer cell proliferation by increasing DNA damage, suppressing ATP production, and accelerating ROS generation synergistically. DOX and LND loaded EVs were also applied to the mouse lung cancer model and exhibited significant anticancer activity. In vivo study showed that smaller EVs exhibited higher anticancer efficiency. In conclusion, the co-delivery of the anticancer drug and the chemosensitizer with EVs may have potential clinical applications for cancer therapy.

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives.

Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons, progressive loss of visual field, and optic nerve atrophy. Autophagy plays a pivotal role in the pathophysiology of glaucoma and is closely related to its pathogenesis. Targeting autophagy and blocking the apoptosis of RGCs provides emerging guidance for the treatment of glaucoma. Here, we provide a systematic review of the mechanisms and targets of interventions related to autophagy in glaucoma and discuss the outlook of emerging ideas, techniques, and multidisciplinary combinations to provide a new basis for further research and the prevention of glaucomatous visual impairment.

Characterization of chloroplast genome of the marine diatom Chaetoceros gracilis.

In the present study, the chloroplast genome of Chaetoceros gracilis was sequenced using the PacBio sequencing platform and phylogenetic analysis was conducted using 38 other complete chloroplast genomes of the Bacillariophyta. The chloroplast genome of C. gracilis was 116,421 bp in length with the typical quadripartite structure, including a large single copy (LSC) region of 61,904 bp, a small single copy (SSC) region of 39,367 bp, and a pair of inverted repeats (IR) regions of 7575 bp. The overall GC content of C. gracilis chloroplast genome was 30.79%. This genome encoded 131 genes incuding 93 protein-coding genes, 30 transfer RNA (tRNA) genes and 8 ribosomal RNA (rRNA) genes. Phylogenetic results exhibited that three Chaetoceros species were clustered together. Chaetoceros gracilis was closely related with Chaetoceros muelleri, and then formed a clade with Chaetoceros simplex with 100% bootstrap value This study will facilitate species identification and study of evolutionary in the family Chaetoceroceae.

Long non-coding RNA DUXAP9 promotes hepatocellular carcinoma cell stemness via directly interacting with sox9.

Long non-coding RNA (LncRNA) DUXAP9 expression was recently found to be higher in hepatocellular carcinoma (HCC) tissues and cells, and correlated with a shorter overall survival of HCC patients. However, its roles in HCC progression have never been revealed. Here, the roles of DUXAP9 in HCC cell stemness are explored as cancer stem cells (CSCs) contribute to one of the root of cancer progression. We found that DUXAP9 positively regulated HCC cell stemness, as characterized by the change of sphere-formation ability, ALDH activity and stemness marker expression. Further luciferase reporter, mRNA stability and RNA-RNA in vitro interaction assays indicated that DUXAP9 directly bound to the 3' untranslated region (UTR) of sox9, enhanced the mRNA stability of sox9 and thus increased sox9 expression. Notably, the effects induced by DUXAP9 on HCC cell stemness depended on sox9 expression. Therefore, this work identifies a novel DUXAP9/sox9 axis essential for HCC cell stemness.

Dendrobium nobile Lindl. alkaloids alleviate Mn-induced neurotoxicity via PINK1/Parkin-mediated mitophagy in PC12 cells.

Modern pharmacological studies have demonstrated that Dendrobium nobile Lindl. Alkaloids (DNLA), the main active ingredients of Dendrobium nobile, is valuable as an anti-aging and neuroprotective herbal medicine. The present study was designed to determine whether DNLA confers protective function over neurotoxicant manganese (Mn)-induced cytotoxicity and the mechanism involved. Our results showed that pretreatment of PC12 cells with DNLA alleviated cell toxicity induced by Mn and improved mitochondrial respiratory capacity and oxidative status. Mn treatment increased apoptotic cell death along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein, all of which were noticeably reversed by DNLA. Furthermore, DNLA significantly abolished the decrease in protein levels of both PINK1 and Parkin, and mitigated the increased expression of autophagy marker LC3-II and accumulation of p62 caused by Mn. These results demonstrate that DNLA inhibits Mn induced cytotoxicity, which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.

Clinical observation of Yiqi Qingdu prescription on the treatment of intermediate-stage and advanced non-small-cell lung cancer.

OBJECTIVE: To observe the effects of the Yiqi Qingdu prescription () on intermediate-stage and advanced non-small-cell lung cancer (NSCLC). METHODS: In total, 300 patients with intermediate-stage or advanced NSCLC were randomly and equally divided into three groups using computer-generated random numbers as follows: Western medicine (WM), Chinese medicine (CM), and integrated Traditional Chinese and Western Medicine (IM). After 3 months of treatment, the overall response rate (ORR); disease control rate (DCR); symptom score (SS); Karnofsky performance status (KPS); adverse event score; counts of CD3 + , CD4 + , and CD8 + cells; CD4 + /CD8 + ratio; and carcinoembryonic antigen (CEA) level were compared among the groups. RESULTS: The ORRs were 30.36% , 20.24% , and 7.87% in the IM, CM, and WM groups, respectively, whereas the DCRs were 85%, 75%, and 73%, respectively. Compared to the CM group, the ORR was significantly higher in the WM and IM groups, whereas the DCR was significantly higher in the IM group (all P < 0.05). SS was obviously higher in the WM group than in the other two groups (both P < 0.01). KPS was significantly lower in the WM group after treatment (P = 0.005). The mean number of adverse events was significantly lower in the CM (2.2 ± 1.3) and IM (2.4 ± 1.3) groups than in the WM group (4.6 ± 1.7, both P < 0.05). CD3 + cell counts were significantly decreased in the WM group (P = 0.031). In the IM group, CD8+ cell counts were increased after treatment, whereas the CD4 + /CD8 + ratio was decreased (both P < 0.01). Compared with the WM group, CD3 + (P = 0.01), CD4 + (P = 0.044), and CD8 + (P = 0.009) cell counts were significantly higher in the IM group, whereas the CD4+ /CD8+ ratio was significantly lower (P = 0.011). Relative to the CM group, CD8 + cell counts were significantly higher (P = 0.001) and the CD4+ /CD8+ ratio was significantly lower in the IM group (P = 0.001). CEA levels were significantly increased in the CM group (P = 0.023). CONCLUSION: The Yiqi Qingdu prescription can improve the outcomes of WM in patients with NSCLC.

LncRNA-ATB Promotes Cisplatin Resistance in Lung Adenocarcinoma Cells by Targeting the miR-200a/ß-Catenin Pathway.

INTRODUCTION: Lung adenocarcinoma (LUAD), which is associated with high morbidity and mortality, is prone to cisplatin resistance, resulting in poor patient prognosis. Long non-coding RNAs (lncRNAs) have complex biological functions in a variety of tumors. Elucidating the underlying molecular mechanisms between lncRNA and cisplatin resistance in LUAD is expected to enable identification of new targets for drug development. METHODS: Cell proliferation was measured by CCK-8 assay and cell apoptosis was detected using flow cytometry analysis. Luciferase reporter assay was conducted to determine the interaction between lncRNA and MicroRNA. Gene expression was evaluated by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction and Western blot analysis. RESULTS: Long non-coding RNA activated by TGF-ß (lncRNA-ATB) was shown to be significantly up-regulated in A549 cells resistant to cisplatin/cis-dichlorodiammineplatinum (II) (cis-DDP) (A549/CDDP cells), compared with corresponding levels in parental A549 cells. Overexpression of lncRNA-ATB significantly elevated cisplatin resistance in LUAD cell lines (A549 and H1975 cells), and this was associated with activation of apoptosis-related genes. Conversely, silencing of lncRNA-ATB decreased cisplatin resistance in LUAD cells. Mechanistically, lncRNA-ATB increased expression of ß-catenin by directly binding to MicroRNA-200a (miR-200a), thereby promoting cell survival and cisplatin resistance. Transfection with a miR-200a mimic or treatment with the ß-catenin downstream pathway inhibitor IWR-1 could reverse the phenotypes induced by lncRNA-ATB overexpression. CONCLUSION: In summary, this study revealed that lncRNA-ATB is dramatically up-regulated in cisplatin-resistant LUAD cell lines, and that lncRNA-ATB facilitates cell survival by targeting the miR-200a/ß-catenin pathway in these cells.

Icariin-mediated activation of autophagy confers protective effect on rotenone induced neurotoxicity in vivo and in vitro.

Rotenone (ROT) is an environmental neurotoxin which has been demonstrated to cause characteristic loss of dopamine (DA) neurons in Parkinson's disease (PD). Icariin (ICA) is a flavonoid glucoside isolated from Herba Epimedii that has been shown to display neuroprotective functions. The present study evaluated protective effects of ICA on ROT-induced neurotoxicity and determined the modulation of ICA on the regulation of autophagy in vivo and in vitro. Rats were treated with ROT (1.0 mg/kg/day) with a co-administration of ICA (15 or 30 mg/kg/day) for 5 weeks. Immunohistochemical analysis showed a significant loss in DA neurons in the substantia nigra (SN) of rats treated with ROT, accompanied by an increase in the accumulation of α-synuclein and a compromised mitochondrial respiration. However, co-administration of ICA potently ameliorated the ROT-induced neuronal cell injury and improved mitochondrial function and decreased the accumulation of α-synuclein. ROT treatment resulted in a decrease in the protein expression of LC3-II and Beclin-1, and an increase in the protein level of P62, and upregulated the activation of mammalian target of rapamycin (mTOR), whereas ICA significantly reversed these aberrant changes caused by ROT. Furthermore, the neuroprotective effect of ICA was further verified in PC12 cells. Cells treated with ROT displayed an increased cytotoxicity and a decreased oxygen consumption which were rescued by the presence of ICA. Furthermore, ROT decreased the protein expression level of LC3-II, enhanced Beclin-1 expression, and activated phosphorylation of mTOR, whereas ICA markedly reversed this dysregulation of autophagy caused by ROT in the PC12 cells. Collectively, these results suggest that ICA mediated activation of autophagic flux confers a neuroprotective action on ROT-induced neurotoxicity.

Icariin protects rotenone-induced neurotoxicity through induction of SIRT3.

Sirtuin-3 (SIRT3) is a mitochondrial NAD + -dependent deacetylase that is essential in regulating mitochondrial proteins and maintaining cellular antioxidant properties. It has been reported that icariin (ICA) is neuroprotective over various neurotoxicant induced oxidative stress. This study aimed to determine whether ICA exerts neuroprotective effects on rotenone (ROT)-induced neurotoxicity through activation of SIRT3. Rats treated with ROT exhibited a marked loss of dopamine (DA) neurons and a decline in motor function, along with a decrease in protein expressions of SIRT3 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the substantia nigra (SN). Administration of ICA significantly alleviated the loss of DA neurons, improved behavioral function, and concomitantly enhanced SIRT3 and PGC-1α expressions. The neuroprotective effect of ICA on ROT-induced cytotoxicity was further confirmed in the PC12 cell model, which showed significant improvement in the survival of ROT-treated cells with ICA pretreatment. The cytoprotective effect of ICA was abolished in ROT-treated cells by SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), along with a resultant decrease in PGC-1α expression. In addition, knockdown of PGC-1α by siRNA suppressed ICA-mediated protective effects but did not affect SIRT3 expression, indicating the role of regulation of PGC-1α by SIRT3 in the protective action of ICA. Furthermore, we showed that ICA improved mitochondrial respiration, oxidative status, enhanced antioxidant enzyme SOD activity and GSH/GSSG ratio in cells treated with ROT. However, these protective effects of ICA on ROT-treated cells was markedly abolished by SIRT3 inhibitor 3-TYP. Our findings demonstrate that ICA exerts a neuroprotective role through upregulation of SIRT3.

Bisphenol A Initiates Excessive Premature Activation of Primordial Follicles in Mouse Ovaries via the PTEN Signaling Pathway.

The essence of primary ovarian insufficiency (POI) is the premature exhaustion of primordial follicles in the follicle pool, which is caused by the excessive premature activation of primordial follicles after birth. Bisphenol A (BPA) exposure promotes the transition of primordial follicles to primary follicles, thus the number of primordial follicles in the primordial follicle pool decreases significantly. However, the molecular mechanisms underlying abnormal follicle activation are poorly understood. Phosphatase and tensin homologue (PTEN) signal system is a negative regulator of follicle activation, which is called the brake of follicle activation. Besides, BPA induces Michigan Cancer Foundation-7 breast cancer cells proliferation by dysregulating PTEN/serine/threonine kinase/p53 axis. Whether BPA initiates the excessive premature activation of primordial follicles in the mouse ovaries via PTEN signaling pathway is unclear. In this study, we treated 6-week-old female CD-1 mice with different concentrations of BPA to study the effect of BPA on follicular activation and development in vivo, as well as the role of PTEN signaling in this process. We observed that BPA in concentrations from 1 µg/kg to 10 mg/kg groups downregulated PTEN expression and initiated excessive premature activation of primordial follicles in the mouse ovaries, and this effect was partly reversible by PTEN overexpression. Our results improve the understanding of both the effect of BPA in occurrence of POI and molecular mechanisms underlying initiation of primordial follicle pool activation, thus providing insight for POI treatment and theoretical basis for reducing the risk of POI.

Analysis of pathological changes of bone hydatid cyst of meriones meridianus after radiotherapy / 中国地方病学杂志

Objective To observe the pathological changes of bone hydatid cyst of meriones meridianus after radiation therapy,and to investigate the clinical effect of radiotherapy on bone hydatid disease.Methods Ascus was dissected sterilely from sheep liver that naturally infected with Echinococcus granulomas,sheared and sac skin removed.Then it was washed and precipitated with 0.9％ sterile saline for 3 times,and scolex was HE stained and counted,from which a 20 ml suspension was made containing 12 × 106/L of scolex.Health meriones meridianus (referred to as gerbil) 140,male and female were in each half,aged 2 to 3 months,body weight(38 ± 6)g,were involved in the study.Gerbil was injected a 0.2 ml suspension containing Echinococcus granulomas scolex into hind tibial periosteum,and X-ray was taken 12 months after the injection.According to the bone destruction in the vaccination site,gerbil hindleg tibia with clear jagged bone destruction was treated as inclusion criteria,and 72 animal were selected as gerbil bone hydatid disease animal models,male and female were in each half.A tatal of 72 gerbils were randomly divided into 4 groups:control group,40 beequerel(Gy) group,50 Gy group and 60 Gy group,18 rats in each group,male and female in each half.The model animals were treated with radiotherapy for 5 times,with 2 d interval,and radiation dose was 300 cGy/min.Each group of gerbils was sacrificed after radiotherapy,bone Echinococcus granulomas cysts was taken out sterilely,and observed by light and electron microscope.Intracapsular cyst fluid was extracted,washed and precipitated with 0.9％ sterile saline repeatedly,and and the pellet was HE stained for observation of scolex morphology and activity by light microscope.Results The morphology and activity ofEchinococcus granulomas in cystic fluid in control group were normal; the morphology and activity of Echinococcus granulomas were still normal in the 40 Gy group,and Echinococcus granulomas was not stained red; but those were abnormal,deformation and atrophy and stained red in the 50 Gy group; and were stained red,deformed,fractured and were wrapped by unknown in the 60 Gy group.By light microscope,the germinal layer,cuticle layer,brood capsule and histological structure of protoscolex were basically normal in irradiated region in the control group.The pathological changes of hydatid cyst in the 40 Gy group were mainly degeneration,structure of hydatid cyst was abnormal,stratum corneum was extensive edema,germinal layer became thinner and the fertile cyst was rare.The main pathological change of hydatid cyst in the 50 Gy group was that corneous layer was widely fractured,and the germinal layer was edema,buckling folds,cells decreased,rare seen brood capsule and scolex; the main pathological changes of hydatid cyst were mainly necrosis in the 60 Gy group,cuticle was extensive fault,stratum corneum and germinal layer was separated,germinal layer was atrophy and disorder,no brood capsule and scolex.By electron microscope,cuticle structure of Echinococcus granulomas cyst was clear,microvillus arranged neatly,morphology and structure of the cell and organelle in cytoplasm were normal in the control group.There were many inflammatory cells infiltrating germinal layer of Echinococcus granulomas cyst,microfilament and contents in microfilament were reduced in the 40 Gy group.Microvillus of Echinococcus granulomas disappeared,nuclear membrane was unclear,endoplasmic and mitochon eclasis,lymphocyte nuclear chromatin was clumping and edge set and in circular permutation in the 50 Gy group.Microvillus disappeared,perinuclear membrane indistinct and ruptured,parts of nucleoli were fragmented and marinated,endoplasmic reticulum was extensive expansion,mitochondria was pyknosis and obvious vacuolization,lymphocyte nuclear chromatin clumping and edge set,lysosomes and macrophage emerge in the 60 Gy group.Conclusions Radiotherapy can destroy the morphology and structure of bone hydatid cyst,radioactivity at 50 Gy has a lethal effect on hydatid cyst.Radiation treatment of bone hydatid disease has a good clinical effect.