The effect of detoxification on acoustic features of Mandarin speech in male heroin users.

This study aims to investigate the effect of detoxification on acoustic features of Mandarin speech. Speech recordings were collected from 66 male abstinent heroin users with different durations of drug detoxification, specifically early abstinent users with a detoxification duration of less than 2 years, sustained abstinent users with 2 years of detoxification, and long-term abstinent users with a detoxification duration of more than 2 years. The results of the acoustic analyses showed that early abstinent users exhibited lower loudness, relative energies of F1, F2, and F3, higher H1-A3, and fewer loudness peaks per second, as well as a longer average duration of unvoiced segments, compared to the sustained and long-term abstinent users. The findings suggest that detoxification may lead to a rehabilitation process in the speech production of abstinent heroin users (e.g., less vocal hoarseness). This study not only provides valuable insights into the effect of detoxification on speech production but also provides a theoretical basis for the speech rehabilitation and detoxification treatment of heroin users.

Status of self-medication and the relevant factors regarding drug efficacy and safety as important considerations among adolescents aged 12-18 in China: a cross-sectional study.

The objective of this study was to investigate self-medication behavior among Chinese adolescents aged 12-18 years and explore the factors associated with whether adolescents prioritize drug efficacy or safety when engaging in self-medication behavior. In 2021, a questionnaire investigation was conducted in the Chinese mainland using a multi-stage sampling approach. After a statistical description, logistic regression was used to analyze the factors associated with considering drug efficacy and safety. The self-medication rate among Chinese adolescents aged 12-18 years was 96.61%. Of these, 65.84% considered drug safety to be essential, while 58.72% prioritized drug efficacy. Regression analysis showed that individuals with better healthcare were more likely to consider drug efficacy an important factor. Additionally, those with a healthier family lifestyle were more likely to prioritize efficacy. When individuals engage in self-medication, those residing in urban areas and possessing advanced preventive health literacy and ample family health resources tend to prioritize drug safety to a greater extent. Conversely, those with higher monthly household incomes and only children exhibit a decreased inclination towards prioritizing safety during self-medication. Self-medication is a frequently observed practice among Chinese adolescents aged 12-18. Several factors, such as demographic and sociological characteristics, health literacy, and family health status, have been found to be associated with the extent to which adolescents prioritize medication safety and efficacy when engaging in self-medication practices. Higher levels of health literacy and better family health status were positively correlated with considering both the efficacy and safety of drugs as important factors when self-medicating.

The perception of Mandarin speech conveying communicative functions in Chinese heroin addicts.

Drug addiction can cause severe damage to the human brain, leading to significant problems in cognitive processing, such as irritability, speech distortions, and exaggeration of negative stimuli. Speech plays a fundamental role in social interaction, including both the production and perception. The ability to perceive communicative functions conveyed through speech is crucial for successful interpersonal communication and the maintaining good social relationships. However, due to the limited number of previous studies, it remains unclear whether the cognitive disorder caused by drug addiction affects the perception of communicative function conveyed in Mandarin speech. To address this question, we conducted a perception experiment involving sixty male participants, including 25 heroin addicts and 35 healthy controls. The experiment aimed to examine the perception of three communicative functions (i.e., statement, interrogative, and imperative) under three background noise conditions (i.e., no noise, SNR [Signal to Noise Ratio] = 10, and SNR = 0). Eight target sentences were first recorded by two native Mandarin speakers for each of the three communicative functions. Each half was then combined with Gaussian White Noise under two background noise conditions (i.e., SNR = 10 and SNR = 0). Finally, 48 speech stimuli were included in the experiment with four options provided for perceptual judgment. The results showed that, under the three noise conditions, the average perceptual accuracies of the three communicative functions were 80.66% and 38% for the control group and the heroin addicts, respectively. Significant differences were found in the perception of the three communicative functions between the control group and the heroin addicts under the three noise conditions, except for the recognition of imperative under strong noise condition (i.e., SNR = 0). Moreover, heroin addicts showed good accuracy (around 50%) in recognizing imperative and poor accuracy (i.e., lower than the chance level) in recognizing interrogative. This paper not only fills the research gap in the perception of communicative functions in Mandarin speech among drug addicts but also enhances the understanding of the effects of drugs on speech perception and provides a foundation for the speech rehabilitation of drug addicts.

Acoustic Characteristics of Mandarin Speech in Male Drug Users.

AIM: Drug use/addiction has a profound impact on the physical and mental health of individuals. Previous studies have indicated that drug users may experience speech perception disorders, including speech illusion and challenges in recognizing emotional speech. However, the influence of drugs on speech production, as another crucial aspect of speech communication, has not been thoroughly examined. Therefore, the current study aimed to investigate how drugs affect the acoustic characteristics of speech in Chinese male drug users. METHOD: Speech recordings were collected from a total of 160 male drug users (including 106 heroin users, 23 ketamine users, and 31 methamphetamine users) and 55 male healthy controls with no history of drug use. Acoustic analysis was conducted on the collected speech data from these groups, and classification analysis was performed using five supervised learning algorithms. RESULTS: The results demonstrated that drug users exhibited smaller F0 standard deviation, reduced loudness, cepstral peak prominence, and formant relative energies, as well as higher H1-A3, longer unvoiced segments, and fewer voiced segments per second compared to the control group. The classification analyses yielded good performance in classifying drug users and non-drug users, with an accuracy above 86%. Moreover, the identification of the three groups of drug users achieved an accuracy of approximately 70%. Additionally, the study revealed different effects on speech production among the three types of drugs. CONCLUSION: The above findings indicate the presence of speech disorders, such as vocal hoarseness, in drug users, thus confirming the assumption that the acoustic characteristics of speech in drug users deviates from the norm. This study not only fills the knowledge gap regarding the effects of drugs on the speech production of Chinese male drug users but also provides a more comprehensive understanding of how drugs impact human behaviors. Furthermore, this research provides theoretical foundations of detoxification and speech rehabilitation for drug users.

Technological achievements in regional economic development: An econometrics analysis based on DEA.

"Double circulation" is an important strategic choice under the development of the new situation. The transformation of university scientific and technological achievements and the coordinated development of regional economy are of great significance to the construction and development of the new paradigm. In this paper, DEA method is used to measure the transformation efficiency of scientific and technological achievements of universities in 31 provinces and autonomous regions (excluding Hong Kong, Macao and Taiwan), and the entropy weight-Topsis model is used to evaluate the quality of regional economic development. The comprehensive scores of the two systems are coupled and coordinated finally. It is found that the transformation efficiency of scientific and technological achievements of universities in 31 provinces and autonomous regions (excluding Hong Kong, Macao and Taiwan) is mostly DEA effective, and the transformation ability of scientific and technological achievements of universities is strong in the regions where university resources are concentrated and the economically developed regions, meanwhile there is a big gap between regions. The transformation ability of scientific and technological achievements in the central and western regions has a big room for improvement. The transformation level of scientific and technological achievements of universities in most provinces is still at a middle level of coordination with the level of regional economic development. In view of the above research conclusions, some countermeasures and suggestions are put forward in order to promote the transformation of scientific and technological achievements and regional economic development can be more coordinated.

The self-medication behaviors of residents and the factors related to the consideration of drug efficacy and safety-A cross-sectional study in China.

Background: Over-the-counter (OTC) drugs facilitates residents self-medication. However, inappropriate self-medications have become a serious problem in China and even all over the world. Objectives: To make an investigation on the current status of Chinese residents' self-medication behaviors and important considerations, and to explore the factors related to the considerations of drug efficacy and safety. Design: A quantitative, cross-sectional study. Methods: Multi-stage sampling was used to conduct a cross-sectional investigation in China 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government. State that an interviewer-administrated questionnaire, was used for data collection. The questionnaire that was used in the investigation included demographic sociological characteristics, health literacy scale-short form (HLS-SF), the 10-item Big Five Inventory (BFI-10), the EuroQol-5D visual analogue scale (EQ-5D VAS), self-medication status and important considerations when self-medicating. Descriptive statistics were performed, and the Chi-square test was used for univariate analysis. Log-binomial regression was used for multivariate analysis on whether residents regard drug efficacy or safety as an important consideration. Results: 9256 respondents were included in the data analysis. The self-medication rate of Chinese adults was as high as 99.1%. Paracetamol and other analgesics were the most common types of OTC medication that respondents purchased, followed by vitamins/minerals. Medical staff recommendations, drug safety and efficacy were the top three important considerations. The residents in the east, central and western regions who consider safety is 63.5%, 61.5%, and 66.8% respectively. The proportion of curative effect was 60.2%, 55.7%, and 61.4% respectively. Log-binomial regression showed that western respondents, retired people, those who mainly used ways including basic medical insurance for employees, commercial medical insurance, free medical treatment to cover their medical cost, respondents with high neuroticism, high health literacy were more likely to consider drug safety as an important factor (p < 0.05). Eastern respondents, employed, main way of medical expenses borne was Out-of-pocket Payment, those with chronic disease were more likely to consider drug efficacy as an important factor (p < 0.05). Female, respondents with high levels of agreeableness, conscientiousness, openness, and self-rated health status were more likely to regard both drug safety and efficacy as important considerations (p < 0.05). Conclusion: Self-medication is practiced by most Chinese adults. Whether Chinese adults take drug efficacy or safety as an important consideration is related to their demographic and sociological characteristics, Big Five personality characteristics, health literacy and self-assessed health status. There is a need to strengthen the management of OTC drugs and public education about self-medication.

Chronic treatment with baicalein alleviates behavioural disorders and improves cerebral blood flow via reverting metabolic abnormalities in a J20 transgenic mouse model of Alzheimer's disease.

Baicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD.

Functional effects of berberine in modulating mitochondrial dysfunction and inflammatory response in the respective amyloidogenic cells and activated microglial cells - In vitro models simulating Alzheimer's disease pathology.

AIM: Berberine (BBR) is an alkaloid extracted from Coptidis Rhizoma, also known as Huang-Lian. Huang-Lian has been used extensively in traditional Chinese medicine for the treatment of various diseases, including diabetes and dementia. Because Alzheimer's disease (AD) is a complex disease that involves various pathophysiological changes, the diverse neuroprotective effects of BBR may be useful for improving the brain's energy state at an early stage of the disease. MAIN METHODS: We performed extracellular flux and 1H NMR-based metabolic profiling analyses to investigate the effects of BBR on metabolic processes in these cells. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist has been studied extensively for the treatment of AD. We explored the combination dosing effects of BBR and PIO in vitro, then leveraged computational methods to explain the experimental finding. KEY FINDINGS: BBR demonstrates potential in modulating the mitochondrial bioenergetics and attenuating dysfunction of the primary energy and glutathione metabolism pathways in an AD cell model. It also suppresses basal respiration and reduces the production of pro-inflammatory cytokines in activated microglial cells. Both experimental and computational observations indicate that BBR and PIO have comparable binding affinities to the PPARγ protein, suggesting both drugs may have some overlapping effects for AD. SIGNIFICANCE: BBR exerts beneficial effects on disrupted metabolic processes in amyloidogenic cells and activated microglial cells, which are important for preventing or delaying early-stage disease progression. The choice of BBR or PIO for AD treatment depends on their respective pharmacokinetic profiles, delivery, efficacy and safety, and warrants further study.

Corrigendum: Deficiency of Mettl3 in Bladder Cancer Stem Cells Inhibits Bladder Cancer Progression and Angiogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.627706.].

Deficiency of Mettl3 in Bladder Cancer Stem Cells Inhibits Bladder Cancer Progression and Angiogenesis.

RNA N6-methyladenosine is a key step of posttranscriptional modulation that is involved in governing gene expression. The m6A modification catalyzed by Mettl3 has been widely recognized as a critical epigenetic regulation process for tumorigenic properties in various cancer cell lines, including bladder cancer. However, the in vivo function of Mettl3 in bladder cancer remains largely unknown. In our study, we found that ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer using transgenic mouse model. In addition, conditional knockout of Mettl3 in K14+ bladder cancer stem cell population leads to inhibition of bladder cancer progression. Coupled with the global transcriptome sequencing and methylated RNA immunoprecipitation sequencing results, we showed that deletion of Mettl3 leads to the suppression of tyrosine kinase endothelial (TEK) and vascular endothelial growth factor A (VEGF-A) through reduced abundance of m6A peaks on a specific region. In addition, the depletion of Mettl3 results in the decrease in both messenger RNA (mRNA) and protein levels of TEK and VEGF-A in vitro. Taken together, Mettl3-mediated m6A modification is required for the activation of TEK-VEGF-A-mediated tumor progression and angiogenesis. Our findings may provide theoretical basis for bladder cancer treatment targeting Mettl3.

Metabolic Profiling of Female Tg2576 Mouse Brains Provides Novel Evidence Supporting Intranasal Low-Dose Pioglitazone for Long-Term Treatment at an Early Stage of Alzheimer's Disease.

Accumulating evidence suggests that disruptions in brain energy metabolism may be a key player in the pathogenesis of Alzheimer's disease (AD). Pioglitazone (PIO) has been found to exert beneficial effects on metabolic dysfunction in many AD preclinical studies. However, limited success in clinical trials remains an obstacle to its development for the treatment of AD. PIO's poor brain penetration was often cited as a contributing factor to the lack of clinical benefit. In this study, we prepared PIO-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and administered them as suspended nanoparticles via nebulization. Preliminary investigation of drug distribution to the brain revealed comparatively reduced systemic exposure after administering PIO nanoparticles via the intranasal route. In vitro, extracellular flux analysis showed significantly raised spare respiratory capacity when cells were treated with low-dose PIO nanoparticles. Tg2576 transgenic mice treated with low-dose PIO nanoparticles over four months exhibited an overall trend of reduced hyperactivity in open field tests but did not show any visible effect on alternation rates in the Y-maze task. Subsequent 1H NMR-based metabolic profiling of their plasma and different brain regions revealed differences in metabolic profiles in the cerebellum, cortex, and hippocampus of Tg2576 mice after long-term PIO treatment, but not in their midbrain and plasma. In particular, the specificity of PIO's treatment effects on perturbed amino acid metabolism was observed in the cortex of transgenic mice with increases in alanine and N-acetylaspartate levels, supporting the notion that PIO treatment exerts beneficial effects on impaired energy metabolism associated with AD. In conclusion, inhalation exposure to PIO nanoparticles presents an exciting opportunity that this drug could be administered intranasally at a much lower dose while achieving a sufficient level in the brain to elicit metabolic benefits at an early stage of AD but with reduced systemic exposure.

In Vitro and In Vivo Comparison of Curcumin-Encapsulated Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles and Curcumin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complexes Administered Intranasally as Therapeutic Strategies for Alzheimer's Disease.

Curcumin (CUR) has antioxidant and anti-inflammatory effects that are beneficial to Alzheimer's disease (AD). However, the poor solubility and high instability of CUR compromise its application greatly. In this study, CUR-encapsulated chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CUR-CS-PLGA-NPs) and hydroxypropyl-ß-cyclodextrin-encapsulated CUR complexes (CUR/HP-ß-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-ß-CD inclusion complexes was stable under physiological conditions over 72 h with 95.41 ± 0.01% remaining, which was higher than 49.66 ± 3.91% remaining in CUR-CS-PLGA-NPs. Meanwhile, CUR/HP-ß-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SY5Y cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 µM CUR in BV-2 cells, which decreased TNF-α and IL-6 levels to approximately 70 and 40%, respectively, when compared to the positive control, respectively. In vivo pharmacokinetic studies indicated that after intranasal administration, the AUC values of CUR in the plasma and brain of the CUR/HP-ß-CD inclusion complex group were 2.57-fold and 1.12-fold higher than those in the CUR-CS-PLGA-NP group at the same dose of 2 mg/kg, respectively. In conclusion, CUR/HP-ß-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.

Nondestructive Strategy to Effectively Enhance the Interfacial Adhesion of PBO/Epoxy Composites.

Low interfacial adhesion seriously limits the wide application of PBO fiber in composites. To solve this problem, a novel hierarchical reinforcement strategy was developed by introducing epoxy sizing, nanoreinforcement of amino-functionalized silicon dioxide (SiO2-NH2), and an interfacial compatibilizer of 2,6-bis(2-hydroxy-4-aminophenyl) benzobisoxazole (HABO) onto poly(p-phenylene benzobisoxazole) (PBO) fibers via a facile dip-coating approach. SiO2-NH2 and HABO were uniformly dispersed in epoxy sizing, forming an active interface layer. On this basis, wettability, surface roughness of the PBO fiber, and compatibility with the resin matrix were significantly improved, which gave 88.4 and 40.4% enhancement in the interfacial shear strength and interlaminar shear strength of the corresponding composites, respectively. Moreover, it should be noted that the outstanding mechanical and thermal properties of the PBO fiber were not impaired during the sizing treatment. In summary, our work provides an effective and damage-free approach to improve the interfacial adhesion of PBO/epoxy composites.

Histone Demethylase KDM4C Is Required for Ovarian Cancer Stem Cell Maintenance.

Ovarian cancer is a highly deadly disease, which is often diagnosed at a late stage with metastases. However, most ovarian cancers relapse after surgery combined with platinum-based chemotherapy. Cancer stem cells (CSCs) are stem-like cells that possess high tumorigenic capability and display higher resistant capability against current therapies. However, our knowledge of ovarian CSCs and their molecular mechanism remains sparse. In the current study, we found that KDM4C, a histone demethylase, was required for ovarian cancer stem cell (CSC) maintenance. Depletion of KDM4C significantly reduced the CSC population and sphere formation in vitro. Moreover, we found that KDM4C can regulate the expression of stem cell factor OCT-4 via binding to its promoter. These data indicate that KDM4C is relevant for ovarian CSC maintenance and underscore its importance as a potential therapeutic target.

First report of Xanthomonas albilineans causing leaf scald on two chewing cane clones in Zhejiang province, China.

In recent years, outbreaks of leaf scald have been reported in two chewing cane clones "Guangdong Huangpi" and "Taoshang Guozhe" in Zhejiang province, China. From May to July 2019, we collected 11 and 13 leaf or stalk samples from symptomatic "Guangdong Huangpi" from four farms in Wenling and "Taoshang Guozhe" clones from three farms in Ruian, Zhejiang province, respectively. Leaves in young plants exhibited white pencil-line streaks (Supplement Fig. 1A & 1D) as well as partial or complete chlorosis of the leaf blade (Supplement Fig. 1B & 1E). Internal symptoms included an orange-red discoloration of the vascular bundles at the basal nodes of the stalk and discoloration extension into the internodes (Supplement Fig. 1C & 1F). Leaf and stalk tissues were used for bacterial isolation and purification on XAS medium, which is selective for Xanthomonas albilineans (Davis et al. 1994), using the streak plate method to obtain 24 isolates (Lin et al. 2018). Circular, convex, smooth, shiny and yellow colonies were isolated from all the samples. The pathogenicity of two isolates, XaCN30 from "Guangdong Huangpi" and XaCN43 from "Taoshang Guozhe", was confirmed with Koch's postulates according to the protocol reported by Lin et al. (2018). The incidences of diseased plants (56% and 63%) were observed in individual host clones at 28 d post-inoculation with isolates XaCN30 and XaCN43, respectively. Furthermore, all isolates were confirmed as X. albilineans via molecular methods. PCR amplification was conducted for all 24 isolates using the primer pairs XgyrB1F/XgyrB1R2 (Ntambo et al. 2019) and XAF1/XAR1 (Wang et al. 1999), which targeting the gyrB (encoding the b subunit of the DNA gyrase) and abc (encoding an ABC transporter) genes, and generating 904 bp and 608 bp amplicons, respectively. The PCR fragments were cloned into the pMD19-T vector (TaKaRa, Dalian, China). For each isolate, three single colonies of transformed Escherichia coli DH5α carrying targeted fragment were sequenced. These sequences were deposited into the GenBank with accession no. MT776053-MT776059 and MT776061-MT776077 for gyrB gene and MT776098-MT776104 and MT776106-MT776122 for abc gene. Based on the two concatenated DNA sequences of our 24 isolates, compared with 27 previously reported X. albilineans isolates obtained from the GenBank database, pairwise sequence identity analysis revealed that all 24 isolates from Zhejiang province had 99.4-100% identity with each other, 99.6-100% identity with 14 published domestic isolates, and 98.3-100% identity with 13 foreign isolates. Furthermore, phylogenetic analysis with MEGA 7.0 (Kumar et al. 2016) showed that the isolates from Zhejiang province clustered into two distinct groups (Supplement Fig. 2). One group consisted of 25 Chinese isolates (including all 11 isolates from Wenling) along with four isolates from the French West Indies (GPE PC73, GPE PC17, GPE PC86, and MTQ032), and one isolate from the USA (XaFL07-1), which were assigned to pulsed-field gel electrophoresis (PFGE) group B (Davis et al. 1997; Pieretti et al. 2012). A putative group was also proposed, which included all 13 isolates from Ruian, indicating that isolates from Ruian are distinct from the isolates isolated from other Chinese sugarcane-planting areas, including Wenling. We conclude that leaf scald disease in local clones of chewing cane are caused by X. albilineans in Zhejiang province in China, which will be helpful for leaf scald management in chewing cane, a cash crop.

Reduced Consolation Behaviors in Physically Stressed Mandarin Voles: Involvement of Oxytocin, Dopamine D2, and Serotonin 1A Receptors Within the Anterior Cingulate Cortex.

BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.

hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer.

PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT.

Reverting Metabolic Dysfunction in Cortex and Cerebellum of APP/PS1 Mice, a Model for Alzheimer's Disease by Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Agonist.

Identification of molecular mechanisms underlying early-stage Alzheimer's disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics approach was employed to investigate the metabolic profiles in plasma and brain tissues harvested from 5-month-old APP/PS1 transgenic mice and their wildtype counterparts. Since different brain regions were expected to have their own distinct metabolic signals, four different brain regions, namely cortex, hippocampus, midbrain and cerebellum tissues, were dissected and had their metabolic profiles studied separately. Biochemical assays were also performed on plasma and brain cortex tissue of transgenic mice and wildtype mice, with a focus on mitochondrial health. Amyloid precursor protein and amyloid-ß levels in plasma, brain cortex tissue and mitochondria fractions isolated from brain cortex were measured to assess the amyloid pathology. Our findings include the observation of extensive metabolic alterations in cortex and cerebellum of APP/PS1 mice, but not in their hippocampus, midbrain and plasma. The major pathways affected in cortex and cerebellum of APP/PS1 mice were closely related to impaired energy metabolism and perturbation of amino acid metabolism in these mice. APP/PS1 mice also exhibited higher amyloid-ß40 and amyloid-ß42 in their cortex, accumulation of mitochondria APP in their cortex, and presented an altered oxidative state in their brain. Treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (PIO) successfully restored the energy metabolism, lowered amyloid-ß levels and afforded the APP/PS1 mice a better antioxidative capacity in their cortex.

Ligand metathesis as rational strategy for the synthesis of cubane-type heteroleptic iron-sulfur clusters relevant to the FeMo cofactor.

Molybdenum-dependent nitrogenases catalyze the transformation of dinitrogen into ammonia under ambient conditions. The active site (FeMo cofactor) is the structurally and electronically complex weak-field metal cluster [MoFe7S9C] built of Fe4S3 and MoFe3S3C portions connected by three sulfur bridges and containing an interstitial carbon atom centered in an Fe6 trigonal prism. Chemical synthesis of this cluster is a major challenge in biomimetic inorganic chemistry. One synthetic approach of core ligand metathesis has been developed based on the design and synthesis of unprecedented incomplete ([(Tp*)WFe2S3Q3]-) and complete ([(Tp*)WFe3S3Q4]2-) cubane-type clusters containing bridging halide (Q = halide). These clusters are achieved by template-assisted assembly in the presence of sodium benzophenone ketyl reductant; products are controlled by reaction stoichiometry. Incomplete cubane clusters are subject to a variety of metathesis reactions resulting in substitution of a µ2-bridging ligand with other bridges such as N3-, MeO-, and EtS- Reactions of complete cubanes with Me3SiN3 and S8 undergo a redox metathesis process and lead to core ligand displacement and formation of [(Tp*)WFe3S3(µ3-Q)Cl3]- (Q = Me3SiN2-, S2-). This work affords entry to a wide variety of heteroleptic clusters derivable from incomplete and complete cubanes; examples are provided. Among these is the cluster [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]-, one of the very few instances of a synthetic Fe-S cluster containing a light atom (C, N, O) in the core, which constitutes a close mimic of the [MoFe3S3C] fragment in FeMo cofactor. Superposition of them and comparison of metric information disclose a clear structural relationship [Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1-)].

[Relationship between vitamin D deficiency and necrotizing enterocolitis in preterm infants].

OBJECTIVE: To evaluate the relationship of vitamin D level with the development of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A total of 429 preterm infants with a gestational age of <36 weeks, who were admitted to the department of neonatology within 2 hours after birth between January and December, 2016, were enrolled in the study. According to whether these infants developed NEC, the 429 subjects were divided into NEC group (n=22) and non-NEC group (n=407). Peripheral venous blood was collected from these preterm infants and their mothers at admission to measure the level of 25-hydroxyvitamin D (25-OHD). The two groups were compared in terms of the serum 25-OHD levels of preterm infants and their mothers. Pearson correlation analysis was used to investigate the correlation between the serum 25-OHD levels of preterm infants and their mothers. The distribution of vitamin D levels in preterm infants was compared between the two groups. The univariate logistic regression analysis was used to determine the risk factors for NEC in preterm infants. RESULTS: The serum 25-OHD levels of preterm infants and their mothers in the NEC group were significantly lower than in the non-NEC group (P<0.001). In both groups, the serum 25-OHD levels of mothers and preterm infants were positively correlated with each other (P<0.001). The distribution of vitamin D levels (normal vitamin D level, low vitamin D level, vitamin D deficiency, and severe vitamin D deficiency) was significantly different between the NEC and non-NEC groups (P<0.001). The univariate logistic regression analysis showed that gestational age, birth weight, 25-OHD levels of preterm infants and their mothers, the duration of mechanical ventilation, the duration of oxygen inhalation, and the length of hospital stay were associated with the development of NEC (P<0.05). CONCLUSIONS: The serum 25-OHD levels of preterm infants and their mothers may be related to the development of NEC in preterm infants, suggesting that vitamin D supplementation during pregnancy is important for preventing the development of NEC in preterm infants.