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Objective: To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients. Methods: This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022. Results: In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication. Conclusion: Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited. [ABSTRACT FROM AUTHOR]

The acquisition of agricultural land is a crucial aspect of survival for numerous rural communities, serving as a fundamental tool for combating poverty and food insecurity and promoting equitable sustainable economic progress. The expropriation of land offers a promising prospect for remedying past inequities and promoting both economic progress and food sufficiency. Limited research has examined the association between land expropriation and food security, livelihood shocks, and the well-being of rural households worldwide. Therefore, this research explores the implications of land expropriation on food security, livelihood shocks, and well-being of land lost rural communities. The data were collected from 384 farmers selected through stratified sampling techniques using face-to-face surveys in rural China. The data were analyzed using descriptive and logit regression models. The descriptive findings showed that land expropriation has detrimental effects on the livelihood, food security, and well-being of the farmers. Furthermore, these impacts are more harmful among land-expropriated households with a lower educational level, a large family size, and women farmers in less developed rural communities. The econometric results evinced that gender, age, education level, marital status, family size, and negative changes in income all significantly affect the impact of land expropriation on the food security of farmers. Similarly, the findings revealed that farmers with lower education levels were more likely to be affected by land loss as compared to farmers with medium and high education levels. Farmers with complete land loss were 1.70 times more likely to suffer livelihood shocks than those with partial land loss. The results also evinced that the well-being of all farmers was not affected equally, and some farmers' well-being was affected more than others due to various socioeconomic backgrounds. Therefore, this study suggests the implementation of public policies that provide support to farmers who have been marginalized due to land acquisition. [ABSTRACT FROM AUTHOR]

Cationic membrane-active toxins are the most abundant group of proteins in the venom of snakes and insects. Cationic proteins such as cobra venom cytotoxin and bee venom melittin are known for their pharmacological reactions including anticancer and antimicrobial effects which arise from the toxin-induced alteration in the dynamics and structure of plasma membranes and membranes of organelles. It has been established that these cationic toxins trigger the formation of non-bilayer lipid phase transitions in artificial and native mitochondrial membranes. Remarkably, the toxin-induced formation of non-bilayer lipid phase increases at certain conditions mitochondrial ATP synthase activity. This observation opens an intriguing avenue for using cationic toxins in the development of novel drugs for the treatment of cellular energy deficiency caused by aging and diseases. This observation also warrants a thorough investigation of the molecular mechanism(s) of lipid phase polymorphisms triggered by cationic proteins. This article presents a review on the application of powerful biophysical methods such as resonance spectroscopy (31P-, 1H-, 2H-nuclear magnetic resonance, and electron paramagnetic resonance), luminescence, and differential scanning microcalorimetry in studies of non-bilayer lipid phase transitions triggered by cationic proteins in artificial and biological membranes. A phenomenon of the triggered by cationic proteins the non-bilayer lipid phase transitions occurring within 10−2–10−11 s is discussed in the context of potential pharmacological applications of cationic proteins. Next to the ATP dimer is an inverted micelle made of cardiolipin that serves as a vehicle for the transport of H+ ions from the intra-crista space to the matrix. It is proposed that such inverted micelles are triggered by the high density of H+ ions and the cationic proteins rich in lysine residue which compete with the conserved lysine residues of the ATP synthase rotor for binding to cardiolipin in the inner mitochondrial membrane and perturb the bilayer lipid packing of cristae. Phospholipids with a blue polar head represent cardiolipin and those with a red polar head represent other phospholipids found in the crista membrane. [ABSTRACT FROM AUTHOR]

The theory of cultural capital has long been applied to explain academic achievement. This qualitative study investigated first-year students in higher vocational colleges and, taking this low cultural capital group as an example, explored how cultural capital has affected their past teacher–student interactions. Participants described their experience of interacting with their teachers. We found that these students primarily experienced authoritative and laissez-faire teacher–student interactions. Students' embodied and institutionalized cultural capital profoundly affected different aspects of the teacher–student interaction. In modern China, vocational and academic education are of the same status, so teachers should modify their evaluations based solely on academic achievement. When interacting with students, teachers should be more understanding and interact in a more student-centred way. Teacher training programmes should also be reformed, and training for teachers in general and vocational schools should be distinguished. [ABSTRACT FROM AUTHOR]

Background: Charcot–Marie–Tooth (CMT) disease is the most frequent hereditary motor sensory neurological disease. GJB1 gene is the second most frequent cause of CMT, accounting for approximately 10% of CMT cases worldwide. We identified a large Han family with X‐linked CMT disease. Methods: In this study, the probands and his mother underwent electrophysiological examinations and other family members were assessed retrospectively. Whole‐exome sequencing, Sanger sequencing, and SNP array linkage analysis were performed to find and confirm the variant. The functional effect of the identified variant was further investigated in HEK293 cells and MCF‐7 cells by minigene splicing assay. Results: The affected individuals had some clinical symptoms including symmetric atrophy and progressive weakness of the distal muscles in their twenties. Electrophysiological examinations result in peripheral nerve injury of the upper and lower limbs. Whole‐exome sequencing identified a novel hemizygous deletion mutation (NM_000166: c.‐16‐8_‐14del) in the GJB1 gene. SNP array linkage analysis and co‐segregation analysis confirmed this mutation. Minigene splicing assay verified that this mutation leads to the activation of cryptic splicing sites in exon 2 which results in the deletion of exon 2. Conclusion: Our study provides theoretical guidance for prenatal diagnosis and subsequent fertility of this family. This result expands the spectrum of mutations in GJB1 known to be associated with CMTX and contributes to the diagnosis of CMT and clinical genetic counseling. [ABSTRACT FROM AUTHOR]

Neutrophils constitute a considerable proportion of all leukocytes found in tumors and are essential for promoting tumor growth. In this issue, Linde et al. demonstrate that an antibody cocktail therapy consisting of tumor necrosis factor (TNF), anti-CD40 monoclonal antibody, and tumor-binding antibody can boost the anti-tumor activity of neutrophils. [ABSTRACT FROM AUTHOR]

The virtual synchronous generator (VSG) improves the robustness of the inverter-interfaced distributed generator (IIDG) against instability by introducing a virtual inertia. However, the transient response of the active power and the angular frequency conflict with each other for the IIDG with fixed inertia control. It is necessary to adopt adaptive control to improve overall performances of power and frequency as the operating condition changes. This paper analyzes the impact of the inertia on power and angular frequency. A dual-adaptivity inertia control strategy is proposed to offer a responsive and stable frequency support and also achieve the balance between power regulation and frequency regulation according to different operating conditions. The principle of parameter design is given to obtain the range of adaptivity. Quantitative assessment considering the cumulative effect of the output deviation and its duration is also presented to evaluate the proposed strategy intuitively. The strategy is further verified based on PSCAD/EMTDC and a hardware-in-loop experiment platform based on RTDS. Results confirm that the proposed strategy not only achieves rapid frequency response with slight dynamic deviations under disturbances but also strikes a balance between the frequency and power and leads to improved overall control. [ABSTRACT FROM AUTHOR]

Xiaoyaosan is a traditional Chinese herbal formula that has long been used to treat liver cirrhosis, liver failure, and hepatocarcinoma (HCC). However, little is known about its mechanism of action and targets in treating chronic liver disease. Aim of the study : This study aimed to detect the critical transition of HCC progression and to explore the regulatory mechanism and targets of Xiaoyaosan treating liver cirrhosis (cirrhosis) using integrative medicinal research involving system biology and pharmacology. We recruited chronic liver disease participants to obtain gene expression data and applied the dynamic network biomarker (DNB) method to identify molecular markers and the critical transition. We combined network pharmacology and DNB analysis to locate the potential DNBs (targets). Then we validated the DNBs in the liver cirrhosis rat models using Xiaoyaosan treatment. The expression of genes encoding the four DNBs, including Cebpa , Csf1, Egfr , and Il7r, were further validated in rat liver tissue using Western blot analysis. We found EGFR , CEBPA , Csf1 , Ccnb1 , Rrmm2 , C3 , Il7r , Ccna2 , and Peg10 overlap in the DNB list and Xiaoyaosan-Target-Disease (XTD) network constructed using network pharmacology databases. We investigated the diagnostic ability of each member in the DNB cluster and found EGFR , CEBPA , CSF1, and IL7R had high diagnostic abilities with AUC >0.7 and P -value < 0.05. We validated these findings in rats and found that liver function improved significantly and fibrotic changes were relieved in the Xiaoyaosan treatment group. The expression levels of CSF1 and IL7R in the Xiaoyaosan group were significantly lower than those in the cirrhosis model group. In contrast, CEBPA expression in the Xiaoyaosan group was significantly higher than that in the cirrhosis model group. The expression of EGFR in the Xiaoyaosan group was slightly decreased than in the model group but not significantly. Using the DNB method and network pharmacology approach, this study revealed that CEBPA , IL7R , EGFR , and CSF1 expression was remarkably altered in chronic liver disease and thus, may play an important role in driving the progression of cirrhosis. Therefore, CEBPA , IL7R , EGFR , and CSF1 may be important targets of Xiaoyaosan in treating cirrhosis and can be considered for developing novel therapeutics. [Display omitted] [ABSTRACT FROM AUTHOR]

Identifying early warning signals of critical transitions during disease progression is a key to achieving early diagnosis of complex diseases. By exploiting rich information of high-throughput data, a novel model-free method has been developed to detect early warning signals of diseases. Its theoretical foundation is based on dynamical network biomarker (DNB), which is also called as the driver (or leading) network of the disease because components or molecules in DNB actually drive the whole system from one state (e.g. normal state) to another (e.g. disease state). In this article, we first reviewed the concept and main results of DNB theory, and then applied the new method to the analysis of type 2 diabetes mellitus (T2DM). Specifically, based on the temporal-spatial gene expression data of T2DM, we identified tissue-specific DNBs corresponding to the critical transitions occurring in liver, adipose and muscle during T2DM development and progression. Actually, we found that there are two different critical states during T2DM development characterized as responses to insulin resistance and serious inflammation, respectively. Interestingly, a new T2DM-associated function, i.e. steroid hormone biosynthesis, was discovered, and those related genes were significantly dysregulated in liver and adipose at the first critical transition during T2DM deterioration. Moreover, the dysfunction of genes related to responding hormone was also detected in muscle at the similar period. Based on the functional and network analysis on pathogenic molecular mechanism of T2DM, we showed that most of DNB genes, in particular the core ones, tended to be located at the upstream of biological pathways, which implied that DNB genes act as the causal factors rather than the consequence to drive the downstream molecules to change their transcriptional activities. This also validated our theoretical prediction of DNB as the driver network. As shown in this study, DNB can not only signal the emergence of the critical transitions for early diagnosis of diseases, but can also provide the causal network of the transitions for revealing molecular mechanisms of disease initiation and progression at a network level. [ABSTRACT FROM AUTHOR]

Abstract: A highly efficient and selective rearrangement reaction of bromohydrins to aldehydes mediated by CF3CO2ZnEt was described. The secondary and tertiary aldehydes were prepared under mild conditions in good to excellent yields (85–99%). The scope and limitations of this rearrangement process were also investigated. [Copyright &y& Elsevier]

Background: The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive. Methods: A case–control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG). A series of rodent and cell line experiments were subsequently used to determine the role and mechanism of secreted adipokines following SG in the alleviation of MASLD. Results: In morbidly obese patients, an increase in circulating Nrg4 levels is associated with the alleviation of hepatic steatosis in the early recovery phase following SG before remarkable weight loss. The temporal parameters of the mice confirmed that an increase in circulating Nrg4 levels was initially stimulated by SG and contributed to the beneficial effect of SG on hepatic lipid deposition. Moreover, this occurred early following bariatric surgery. Mechanistically, gain- and loss-of-function studies in mice or cell lines revealed that circulating Nrg4 activates ErbB4, which could positively regulate fatty acid oxidation in hepatocytes to reduce intracellular lipid deposition. Conclusions: This study demonstrated that the rapid effect of SG on hepatic lipid metabolic reprogramming mediated by circulating Nrg4 alleviates MASLD. [ABSTRACT FROM AUTHOR]

Inverter-interfaced distributed generators (IIDGs) have been widely applied due to their control flexibility. The stability problems of IIDGs under large signal disturbances, such as large load variations and feeder faults, will cause serious impacts on the system. The virtual synchronous generator (VSG) control is an effective scheme for IIDGs to increase transient stability. However, the existing linearized stability models of IIDGs are limited to small disturbances. Hence, this paper proposes a Lyapunov approach based on non-linearized models to assess the large signal stability of VSG-IIDG. The electrostatic machine model is introduced to establish the equivalent nonlinear model. On the basis of Popov's theory, a Lyapunov function is derived to calculate the transient stability domain. The stability mechanism is revealed by depicting the stability domain using the locus of the angle and the angular frequency. Large signal stability of the VSG-IIDG is quantified according to the boundary of the stability domain. Effects and sensitivity analysis of the key parameters including the cable impedance, the load power, and the virtual inertia on the stability of the VSG-IIDG are also presented. The simulations are performed in PSCAD/EMTDC and the results demonstrate the proposed large signal stability assessment method. [ABSTRACT FROM AUTHOR]

Abstract GIN (GFP-expressing inhibitory interneuron) transgenic mice are believed to express the enhanced GFP (eGFP) in a subset of somatostatin (SST)-expressing interneurons in the neocortex and have been widely used in the study on SST interneurons. Previous studies showed that eGFP+ neurons in the neocortex are distributed in the layer II-IV and upper layer V (cortical eGFP neurons) and contain SST. In this study, we reported a new group of eGFP+ neurons in GIN mice at early postnatal ages, which was located in the deep layer of the lateral neocortex as clusters (cluster eGFP neurons). Cluster eGFP neurons were noticeable at birth but disappeared within two months, in contrast to cortical eGFP neurons that started to appear around postnatal day 3 to 5 and existed through life. Cluster eGFP neurons were not immunoreactive for SST antibodies, contrary to cortical eGFP neurons. They were also not immunolabeled by parvalbumin, a marker for another major type of interneurons, and Ca2+/calmodulin-dependent kinases II, a commonly used marker for excitatory neurons. Firing rate, afterhyperpolarization, and excitatory synaptic activity significantly enhanced in cortical eGFP neurons during postnatal development, but these properties remained mostly unchanged in cluster eGFP neurons. Short-term plasticity of the excitatory synapse showed robust facilitation in cortical eGFP neurons but depression in cluster eGFP neurons. These results implied that eGFP might also be expressed in other types of cortical neurons in addition to SST-containing interneurons in GIN mice at early postnatal ages. Highlights • A new group of eGFP+ neurons, in addition to the previously reported one, is present in the neocortex of GIN mice. • Those eGFP+ neurons are distributed in the deep cortical layers as clusters and disappear mostly after the second postnatal month. • They are not immunoreactive for SST, PV, GAD, and CaMKII antibodies. • They display distinct intrinsic and synaptic properties and postnatal development. [ABSTRACT FROM AUTHOR]

Objectives: Autosomal-dominant hypocalcification amelogenesis imperfecta (ADHCAI) is a hereditary disease characterized by enamel defects. ADHCAI is mainly caused by nonsense mutations in a gene called family with sequence similarity 83 member H (FAM83H). To study the pathogenesis of ADHCAI, a Chinese ADHCAI family was investigated. Materials and methods: The ultrastructure of enamel was analyzed by micro-CT and scanning electron microscopy. Whole-exome sequencing (WES) was performed to identify the pathogenic gene. The function of the mutant FAM83H was studied by real-time PCR, western blotting, subcellular localization, and protein degradation pathway analyses. Results: WES identified a known nonsense mutation (c.1915A > T) in exon 5 of the FAM83H gene, causing a truncated protein (p.Lys639*). However, the cases reported herein exhibited significant differences in the clinical phenotype compared with that the previously reported case. An abnormal enamel rod head structure was observed in affected teeth. In vitro functional studies showed altered protein localization and a decreased protein degradation rate for mutant FAM83H. Conclusions: We verified the FAM83H p.Lys639* protein as a gain-of-function variant causing ADHCAI. Abnormal enamel rod head structure was observed in teeth with mutant FAM83H proteins. We also investigated the molecular pathogenesis and presented data on the abnormal degradation of mutant FAM83H proteins. Clinical relevance: This study helped the family members to understand the disease progression and provided new insights into the pathogenesis of ADHCAI. Due to the large heterogeneity of ADHCAI, this study also provided a genetic basis for individuals who exhibit similar clinical phenotypes. [ABSTRACT FROM AUTHOR]

Our previous studies have revealed that a dominant mutation in vacuolar protein sorting 4B (VPS4B), a member of the AAA ATPase family, causes dentin dysplasia type I. The purpose of the present study was to investigate the roles of VPS4B in human dental pulp stem cells (hDPSCs) and to elucidate the underlying molecular mechanisms. In this study, we found that VPS4B was highly expressed in the dental pulp cells of the mouse molar tooth germ, and the expression of VPS4B increased significantly during the odontoblastic differentiation of hDPSCs. VPS4B downregulation inhibited the proliferation, migration, and odontoblastic differentiation of hDPSCs. Moreover, treatment with lithium chloride, an agonist of the Wnt-β-catenin signalling pathway, partially reversed the VPS4B knockdown-driven suppression of proliferation and of odontoblastic differentiation of hDPSCs. Collectively, our findings indicate that VPS4B, via Wnt-β-catenin signalling, acts as a regulator of the proliferation and differentiation of hDPSCs. Our results suggest potential therapeutic avenues for dentin formation and regenerative endodontics in patients with dentin dysplasia type I. [ABSTRACT FROM AUTHOR]

Abstract LIM homeobox transcription factor 1, alpha (LMX1A) is downregulated in human gastric cancer (GC), functioning as a tumor suppressor. The current study aims to identify specific microRNA that can regulate LMX1A expression. By sequence analysis of LMX1A mRNA 3′-untranslated region (3′-UTR), we show that microRNA-9 (miR-9) putatively targets human LMX1A. In established (AGS cells) and primary human GC cells, ectopic overexpression of miR- 9 by a lentiviral construct decreased LMX1A 3′-UTR activity, causing LMX1A mRNA and protein downregulation. Functional analyses show that miR-9 overexpression enhanced GC cell survival and proliferation. On the contrary, miR-9 inhibition by antagomir-9 lentivirus increased LMX1A 3′-UTR activity to upregulate LMX1A mRNA and protein expression, causing GC cell apoptosis. CRISPR/Cas9-mediated LMX1A knockout promoted AGS cell survival and proliferation. Importantly, miR-9 and antagomiR-9 were ineffective to the function of LMX1A-knockout AGS cells. In human GC tissues miR-9 is upregulated, which is negatively correlated with LMX1A downregulation. Together, we conclude that miR-9 selectively targets LMX1A to promote GC cell progression. Highlights • miR-9 overexpression downregulates LMX1A, promoting gastric cancer (GC) cell proliferation. • miR-9 inhibition upregulates LMX1A to induce GC cell apoptosis. • LMX1A is the direct and primary target of miR-9 in GC cells. • miR-9 upregulation in human GC tissues correlates with LMX1A downregulation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Zero-added conversion of chicken manure into water treatment catalyst (RCM) is realized. • Electron-poor/rich microregions are successfully constructed on RCM. • Pollutant degradation processes can be driven by a little bit of peroxymonosulfate. • RCM has excellent performance on actual wastewater treatment. • Water treatment with low consumption is achieved by utilization of pollutants. Fecal pollution in rural areas and water pollution caused by emerging contaminants (ECs) are two international environmental problems. Here, we propose a new strategy to address the two problems simultaneously through the resource utilization and harmless transformation of poultry manure as a kind of water purification catalyst with zero addition. The ordered bonding of intrinsic metal-organic species is realized in the resourcelized procedure by a one-stage calcination-annealing method, which results in the formation of electron-rich/poor microregions. With the triggering of a small amount of peroxymonosulfate (PMS), the energy/electrons of ECs are utilized by the dissolved oxygen in water driven by the electron-rich/poor microregions on the catalyst surface. As a result, the system exhibits excellent performance in removing various ECs. The degradation rate can even be maintained above 94.3 % after 10,000 cycles. This work indicates a sustainable approach to the effective utilization and treatment of rural waste and pollutants. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Dehydration on admission is correlated with neurological deterioration (ND). The primary objective of our study was to use support vector machine (SVM) algorithms to identify an ND prognostic model, based on dehydration equations. Methods: This study included a total of 382 patients hospitalized with acute ischemic stroke. The following parameters were recorded: age, sex, laboratory values (serum sodium, potassium, chlorinum, glucose, and urea), and vascular risk factor data. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative performance of the BUN/Cr ratio as well as each of 38 equations for predicting ND. We used the Boruta algorithm for feature selection. After optimizing the SVM kernel parameters, we built an SVM model to predict ND and used the test set to obtain predictive values for assessing model accuracy. Results: In total, 102 of 382 patients (26.7%) with acute ischemic stroke developed ND. In all patients, the BUN/Cr ratio and each of 38 equations were significant predictors of ND. Equation 20 [1.86 × Na+ + glucose + urea + 9] yielded the maximum area under the ROC curve, and faired best in terms of prognostic performance (a cutoff value of 284.49 mM yielded a sensitivity of 94.12% and specificity of 61.43%). Equation 32 predicted ND poststroke across population groups, and worked well in older as well as young adults; (a cutoff value of 297.08 mM yielded a sensitivity of 93.14% and specificity of 60.00%). Feature selection by the Boruta algorithm was used to decrease the number of variables from 18 to 5 in the condition. The specificity of test samples for the SVM prediction model increased from 44.1% to 89.4%, and the AUC increased from 0.700 to 0.927. Conclusions: SVM algorithms can be used to establish a prediction model for dehydration‐associated ND, with good classification results. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which targets histone H3 lysine 27. Studies have reported that EZH2 is involved in the development of several types of tumor, including ovarian cancer. p16, a well‑known cell cycle regulator, has been demonstrated to be a tumor suppressor gene in a variety of malignant cells. However, the regulatory association between EZH2 and p16 in ovarian cancer remains to be fully elucidated. The present study aimed to determine whether EZH2 is involved in the development of ovarian cancer by regulating the expression of p16. An EZH2 short hairpin RNA (shRNA) lentiviral vector was constructed and used for transducing A2780 and SKOV3 ovarian cancer cell lines. The expression levels of EZH2 and p16 in the ovarian cancer cells were detected using a reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The function of the inhibition of EZH2 in cell proliferation and migration were determined using a CCK‑8 assay and Transwell assay. In addition, a nude mouse xenograft model was used to determine the function of EZH2 and p16 in the formation of ovarian cancer in vivo. The results revealed that the inhibition of EZH2 increased the expression of p16, and suppressed the proliferation and migration capabilities of ovarian cancer in vitro. The downregulated expression of EZH2 suppressed ovarian tumor formation in vivo. The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNAs (miRNAs) exhibit dysregulated expression in human cancer and play an important role in carcinogenesis. The aim of this study was to identify a distinct miRNA expression signature for cervical cancer and cervical intraepithelial neoplasia (CIN) and to investigate the function of deregulated miRNAs in cervical carcinoma. Methods: A miRNA microarray was used to compare miRNA expression profiles in cervical cancer, CIN and normal cervical tissues. Real-time RT-PCR was used to validate the expression of 9 miRNAs in 103 cervical tissues. Bioinformatics programs were used to predict potential target genes and their function. Functional studies were performed to characterize the effect on cervical cancer cells by overexpression of miR-218 and miR-21. Results: We identified deregulated miRNAs in cervical cancer and high-grade squamous intraepithelial lesions (HSIL). MiR-218 was the most downregulated (0.175-fold decrease) miRNA, and miR-21 was the most upregulated (5.67-fold increase) miRNA. In addition, the expression patterns of 9 miRNAs were validated by real-time RT-PCR. Bioinformatics analyses and functional studies indicated that miR-218 and miR-21 may be involved in cancer invasion and metastasis. Conclusion: Our study demonstrated that miRNAs are aberrantly expressed in cervical cancer and cervical preneoplastic lesions. These miRNAs may be involved in the progression of cervical neoplasm as potential tumor suppressor genes or oncogenes. [ABSTRACT FROM AUTHOR]

Antagonists of the group II metabotropic glutamate (mGlu) 2/3 receptors have been shown to have a rapid antidepressant effect. GABAergic interneurons play a crucial role in major depressive disorder (MDD) and possibly mediate the rapid antidepressant effect. However, how mGlu2/3 receptors regulate synaptic activities to GABAergic interneurons is not fully understood. In the present work, we studied the effect of mGlu2/3 receptors on excitatory and inhibitory synaptic activities to somatostatin (SST)- and parvalbumin (PV)-expressing interneurons, two major types of GABAergic interneurons, in the anterior cingulate cortex (ACC) that is strongly indicated in MDD. We found that activation of mGlu2/3 receptors by (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl) glycine (DCG-IV), an agonist of mGlu2/3 receptors, remarkably reduced the frequency, but not the amplitude, of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) and the amplitude of evoked EPSCs in both types. The reduction in the frequency of sEPSCs and the amplitude of evoked EPSCs was more pronounced in SST interneurons. DCG-IV, however, did not affect spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) and evoked IPSCs in both types. LY341495, an antagonist of mGlu2/3 receptors, enhanced the amplitude of evoked EPSCs without affecting sEPSCs and mEPSCs in both types. It also did not affect sIPSCs and evoked IPSCs except slightly increasing the frequency of mIPSCs in SST interneurons. Our results indicate that mGlu2/3 receptors primarily regulate excitatory synaptic activities to the two types of GABAergic interneurons in the ACC. • DCG-IV reduced excitatory, but not inhibitory, synaptic activities to SST and PV interneurons in the ACC. • The reduction of excitatory synaptic activities by DCG-IV was more pronounced in SST interneurons. • LY341495 enhanced the amplitude of evoked EPSCs but did not affect sEPSCs and mEPSCs in SST and PV interneurons. • LY341495 did not affect inhibitory synaptic activities to SST and PV interneurons. [ABSTRACT FROM AUTHOR]

Background: In traditional Chinese medicine (TCM) clinical practice, TCM syndromes help to understand human homeostasis and guide individualized treatment. However, the TCM syndrome changes with disease progression, of which the scientific basis and mechanism remain unclear. Methods: To demonstrate the underlying mechanism of dynamic changes in the TCM syndrome, we applied a dynamic network biomarker (DNB) algorithm to obtain the DNBs of changes in the TCM syndrome, based on the transcriptomic data of patients with chronic hepatitis B and typical TCM syndromes, including healthy controls and patients with liver-gallbladder dampness-heat syndrome (LGDHS), liver-depression spleen-deficiency syndrome (LDSDS), and liver-kidney yin-deficiency syndrome (LKYDS). The DNB model exploits collective fluctuations and correlations of the observed genes, then diagnoses the critical state. Results: Our results showed that the DNBs of TCM syndromes were comprised of 52 genes and the tipping point occurred at the LDSDS stage. Meanwhile, there were numerous differentially expressed genes between LGDHS and LKYDS, which highlighted the drastic changes before and after the tipping point, implying the 52 DNBs could serve as early-warning signals of the upcoming change in the TCM syndrome. Next, we validated DNBs by cytokine profiling and isobaric tags for relative and absolute quantitation (iTRAQ). The results showed that PLG (plasminogen) and coagulation factor XII (F12) were significantly expressed during the progression of TCM syndrome from LGDHS to LKYDS. Conclusions: This study provides a scientific understanding of changes in the TCM syndrome. During this process, the cytokine system was involved all the time. The DNBs PLG and F12 were confirmed to significantly change during TCM-syndrome progression and indicated a potential value of DNBs in auxiliary diagnosis of TCM syndrome in CHB. Trial registration Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (http://www.clinicaltrials.gov) [ABSTRACT FROM AUTHOR]