High-Performance Diamond Phototransistor with Gate Controllable Gain and Speed.

This paper presents a fabricated solar-blind phototransistor based on hydrogen-terminated diamond. The phototransistor shows a large photocurrent and enhancement of responsivity over conventional two-terminal diamond-based photodetector. These enhancement effects are owing to the internal gain of the phototransistor. The fabricated phototransistor exhibits a high photoresponsivity (R) of 2.16 × 104 A/W and a detectivity (D*) of 9.63 × 1011 jones, with gate voltage (VG) and drain voltage of approximately -1.5 V and -5 V, respectively, under 213 nm light illumination. Even at ultralow operating voltage of -0.01 V, the device records satisfactory performance with R and D* of 146.7 A/W and 6.19 × 1010 jones, respectively. By adjusting the VG, photocurrent generation in the device can be continuously tuned from the fast photoconductive effect to the optical gating effect with high optical gain. When VG increases from 1.4 to 2.4 V, the decay time decreases from 1512.0 to 25.5 ms. Therefore, responsivity, dark current, Iphoto/Idark, and decay time of the device can be well tuned by VG.

A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood.

Background: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level. Objective: This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children. Methods: A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets. Results: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets. Conclusions: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Transcutaneous electrical acupoint stimulation improves endometrial receptivity resulting in improved IVF-ET pregnancy outcomes in older women: a multicenter, randomized, controlled clinical trial.

OBJECTIVE: To examine the effects and mechanisms of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization (IVF)-embryo transfer (ET). DESIGN, SETTING, AND PARTICIPANTS: This efficacy study was a multicenter, randomized, controlled clinical trial (RCT) in women receiving IVF-ET. The mechanistic study was a single-center RCT. INTERVENTIONS: The participants received TEAS vs. no TEAS treatment. MAIN OUTCOME MEASURES: In the efficacy study, the primary outcomes were the rates of clinical pregnancy, embryo implantation, and live birth. In the mechanistic study, sex hormones and endometrial protein expression were examined. RESULTS: Ultimately, 739 participants were enrolled (367 and 372 in the TEAS and control groups, respectively). The clinical pregnancy rate was higher in the TEAS group than in the controls (55.1% vs. 46.7%, P = 0.03). There were no significant differences in embryo implantation, biochemical pregnancy, and live birth rates between the two groups (all P > 0.05) in the study population. In women > 35 years, the clinical pregnancy rates, embryo implantation rates and live birth rates in the TEAS and control groups were 48.9% vs. 23.7% (P = 0.004),30.8 vs. 13.9% (P = 0.001) and 34.0% vs. 19.7% (P = 0.06) respectively. In the mechanistic study with 120 participants, on the theoretical embryo implantation day, better developed endometrial pinopodes, elevated endometrial integrin α1ß1/αVß3, leukemia inhibitory factor, and elevated serum progesterone levels were found in the TEAS group compared with controls. CONCLUSION: TEAS significantly improved the clinical pregnancy rate in women undergoing IVF-ET, especially in women of older age. It might be due to improved endometrial receptivity. TRIAL REGISTRATION: ChiCTR-TRC-13003950.

Associations of essential element serum concentrations with autism spectrum disorder.

This case-control study explored the associations between autism spectrum disorder (ASD) and the serum concentration of nine chemical elements in children. The study recruited 92 Chinese children with ASD and 103 typically developing individuals. Serum concentrations of nine chemical elements (calcium, iodine, iron, lithium, magnesium, potassium, selenium, strontium, and zinc) were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). An unconditional logistic regression model was used to analyze the associations between the serum concentrations of the elements and the risk of ASD. After adjusting for confounders, the multivariate analysis results showed that zinc ≤ 837.70 ng/mL, potassium > 170.06 µg/mL, and strontium ≤ 52.46 ng/mL were associated with an increased risk of ASD, while selenium > 159.80 ng/mL was associated with a decreased risk of ASD. Furthermore, the degree of lithium and zinc deficiency was associated with ASD severity. The results indicated that metallomic profiles of some specific elements might play important roles in the development of ASD, a finding of scientific significance for understanding the etiology, and providing dietary guidance for certain ASD types.

Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain.

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by µ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the µ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

The salience of competing nonsocial objects reduces gaze toward social stimuli, but not the eyes, more in typically developing than autistic boys.

Decreased attention to social information is considered an early emerging symptom of autism spectrum disorder (ASD), although the underlying causes remain controversial. Here we explored the impact of nonsocial object salience on reduced attention to social stimuli in male ASD compared with typically developing (TD) children. Correlations with blood concentrations of neuropeptides linked with social cognition were also investigated. Eye-tracking was performed in 102 preschool-aged boys (50 ASD, 52 TD) using a paradigm with social (faces) versus nonsocial (objects) stimuli presented in pairs in two conditions where nonsocial stimulus salience was varied. Basal oxytocin (OXT) and vasopressin concentrations were measured in blood. Compared with TD boys those with ASD viewed social stimuli less only when they were paired with low-salience nonsocial objects. Additionally, boys with ASD spent less time than TD ones viewing facial features, particularly the eyes. In TD boys, OXT concentrations and cognitive development scores were positively associated with time spent viewing the eye region, whereas for boys with ASD associations with time spent viewing faces were negative. Reduced gaze toward social stimuli in ASD relative to TD individuals may therefore be influenced by how salient the paired nonsocial objects are for the latter. On the other hand, reduced interest in the eyes of faces in boys with ASD is not influenced by how salient competing nonsocial stimuli are. Basal OXT concentrations and cognitive development scores are predictive of time spent viewing social stimuli in TD boys (eyes) and those with ASD (faces) but in the opposite direction. LAY SUMMARY: Children with autism exhibit reduced attention to social paired with nonsocial stimuli compared to typically developing children. Using eye-tracking we show this difference is due to typically developing rather than autistic boys being more influenced by how interesting competing nonsocial objects are. On the other hand, reduced time looking at the eyes in autistic relative to typically developing boys is unaffected by nonsocial object salience. Time spent viewing social stimuli is associated with cognitive development and blood levels of oxytocin.

Association Between Essential Metal Elements and the Risk of Autism in Chinese Han Population.

Essential metal elements (EMEs) have essential roles in neurological development and maintenance of human homeostasis. We performed a case-control study to explore association between the risk of autism spectrum disorder (ASD) and the 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum. Ninety-two autistic subjects (cases) and age-sex-matched healthy subjects (controls = 91) from Beijing, China were recruited. In addition, totally 109 mothers of recruited children participated in this study. ICP-AES and ICP-MS were applied to determine the concentration of 11 EMEs in serum. The concentrations of Ca, K, and Mg were significantly higher in the cases than in the controls (OR [95% CI]: 1.031 [1.006-1.058] for Ca; 1.081 [1.046-1.118] for K; 1.161 [1.012-1.331] for Mg), while the concentrations of Zn and Cu were significantly lower (0.997 [0.995-0.999] for Cu; 0.996 [0.992-1.000] for Zn). Clear dose-response relationships between EMEs concentrations and the risk of ASD, as well as the correlation between EME concentrations and the severity of ASD were observed for most of the above EMEs. Six and seven specific correlated pairs between mothers and children were found in the cases and controls separately. The overall profiles of the EMEs were changed in the cases as compared to the controls. This study suggested that the higher levels of Ca, K, and Mg and lower levels of Zn and Cu may be associated with an elevated risk of ASD.

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

LAY ABSTRACT: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.

Postnatal AVP treatments prevent social deficit in adolescence of valproic acid-induced rat autism model.

Studies have shown that arginine-vasopressin (AVP) is an important neuropeptide regulating social behaviors. The present work aimed to detect changes in the AVP numbers and level in a valproic acid (VPA)-induced rat model of autism and the underlying mechanism of its pathogenesis. Our results indicated that infants exposed to VPA showed obviously impaired communication and repetitive behaviors with reduced number of AVP-ir cells in paraventricular nucleus (PVN) and cerebrospinal fluid (CSF). The postnatal subcutaneous injection of AVP can alleviate social preference deficits and stereotyped behaviors, accompanied with the increase of the AVP concentrations in the CSF. We concluded that AVP system was involved in etiology of VPA-induced autism-like symptoms and postnatal AVP treatment rescued the behavioral deficits,which could be a promising treatment for autism.

Acupuncture and Related Techniques for Pain Relief and Treatment of Heroin Addiction: Mechanisms and Clinical Application.

A neurochemical hypothesis of acupuncture analgesia suggests that the pain relief effect of acupuncture is primarily due to activation of a central endorphin system. It has been shown that the primary afferent sensory fibers, a mesolymbic neural circuit, and a descending inhibitory pathway are critical in acupuncture analgesia. The therapeutic effects of electroacupuncture (EA) and related techniques, such as transcutaneous electroacupoint stimulation (TEAS), are frequency-dependent: different frequencies of EA activate different brain regions and release different neuropeptides. EA and TEAS have been used successfully to treat heroin addiction. Activation of endorphin gene expression and release by TEAS can explain the dramatic attenuation of withdrawal syndrome and prolongation of retention time during and after detoxification treatment in patients who are addicted to heroin. However, repeated EA at high intensity should be avoided because it can induce a gradual loss of the analgesic effect. Opioid-receptor desensitization occurs and is manifested as decreased ligand-binding affinity and second-messenger detachment. Repeated large doses of morphine induce morphine tolerance. Cross-tolerance between morphine and EA suggests similar underlying mechanisms. Recent studies have demonstrated that excessive activation of cholecystokinin (CCK), an antiopioid peptide, appears to be responsible. CCK-receptor subtype B (CCKBR) and opioid µ-receptor are co-expressed in the dorsal-horn neurons. Activation of CCKBR promotes formation of heteromerization of morphine-receptor and CCKBR. Interaction of the third transmembrane domain between the 2 receptors resulted in the reduced binding affinity of the opioid receptor.

Pain Relief during Oocyte Retrieval by Transcutaneous Electrical Acupoint Stimulation: A Single-Blinded, Randomized, Controlled Multicenter Trial.

Acupuncture has pain-relief effects, but no data were available on the use of transcutaneous electric acupoint stimulation (TEAS) in pain relief during oocyte retrieval. This study was designed to examine the effect of TEAS for pain relief in women undergoing transvaginal ultrasound-guided oocyte aspiration. This single-blinded, multicenter, randomized controlled trial was performed in China between May 2013 and May 2015. The subjects were randomized to mock TEAS and TEAS. TEAS or mock TEAS was administered 30 min before oocyte retrieval until the end of the operation. The primary and secondary endpoints were the pain measured using the visual analog scale (VAS) within 1 min and 1 hour after oocyte retrieval, respectively. Serum ß-endorphin levels were tested in the first 50 patients/group. 390 women were undergoing oocyte retrieval. Pain levels evaluated using VAS within 1 min (18.6 ± 1.3 vs. 24.4 ± 1.7, P < 0.01) and 1 h after oocyte aspiration (4.6 ± 0.7 vs. 6.8 ± 0.8, P < 0.05) were lower in the TEAS group than in the mock TEAS group. Nausea assessment revealed a significantly lower VAS score in the TEAS group within 1 min (1.2 ± 0.4 vs. 2.9 ± 0.7, P < 0.033). Serum ß-endorphin levels were significantly higher in the TEAS group than in the mock TEAS group (11.4 ± 0.5 vs. 9.1 ± 0.4, P < 0.001) after retrieval. Serum ß-endorphin levels were higher in the TEAS group after the procedure than baseline (11.4 ± 0.5 vs. 9.1 ± 0.3, P < 0.001). Oocyte retrieval causes pain and discomfort, but TEAS is effective and safe for suppressing the pain and alleviating nausea associated with the operation.

Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats.

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aß and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aß fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

High temperature silicon-carbide-based flexible electronics for monitoring hazardous environments.

With its unprecedented properties over conventional rigid platforms, flexible electronics have been a significant research topic in the last decade, offering a broad range of applications from bendable display, flexible solar-energy systems, to soft implantable-devices for health monitoring. Flexible electronics for harsh and hazardous environments have also been extensively investigated. In particular, devices with stretchability and bend-ability as well as tolerance to extreme and toxic operating conditions are imperative. This work presents silicon carbide grown on silicon and then transferred onto polyimide substrate as a new platform for flexible sensors for hostile environments. Combining the excellent electrical properties of SiC and high temperature tolerance of polyimide, we demonstrated for the first time a flexible SiC sensors that can work above 400 °C. This new sensing platform opens exciting opportunities toward flexible sensing applications in hazardous environments.

Transcutaneous Electrical Acupoint Stimulation in Early Life Changes Synaptic Plasticity and Improves Symptoms in a Valproic Acid-Induced Rat Model of Autism.

Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficit in childhood without satisfactory medical intervention. Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive technique derived from acupuncture and has been shown to have similar therapeutic effects in many diseases. Valproic acid- (VPA-) induced ASD is a known model of ASD in rats. The therapeutic efficacy of TEAS was evaluated in the VPA model of ASD in the present study. The offspring of a VPA-treated rat received TEAS in the early life stage followed by a series of examinations conducted in their adolescence. The results show that following TEAS treatment in early life, the social and cognitive ability in adolescence of the offspring of a VPA rat were significantly improved. In addition, the abnormal pain threshold was significantly corrected. Additional studies demonstrated that the dendritic spine density of the primary sensory cortex was decreased with Golgi staining. Results of the transcriptomic study showed that expression of some transcription factors such as the neurotrophic factor were downregulated in the hypothalamus of the VPA model of ASD. The reduced gene expression was reversed following TEAS. These results suggest that TEAS in the early life stage may mitigate disorders of social and recognition ability and normalize the pain threshold of the ASD rat model. The mechanism involved may be related to improvement of synaptic plasticity.

Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion.

Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11-21 of Shank3, leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3-deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3-depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3-deficient rats. It is worth to note that Shank3-deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3-related neurodevelopmental disorders.

Description and Verification of the Fundamental Current Mechanisms in Silicon Carbide Schottky Barrier Diodes.

Attempts to model the current through Schottky barrier diodes using the two fundamental mechanisms of thermionic emission and tunnelling are adversely impacted by defects and second order effects. This has led to the publication of countless different models to account for these effects, including some with non-physical parameters. Recently, we have developed silicon carbide Schottky barrier diodes that do not suffer from second order effects, such as excessive leakage, carrier generation and recombination, and non-uniform barrier height. In this paper, we derive the foundational current equations to establish clear links between the fundamental current mechanisms and the governing parameters. Comparing these equations with measured current-voltage characteristics, we show that the fundamental equations for tunnelling and thermionic emission can accurately model 4H silicon carbide Schottky barrier diodes over a large temperature and voltage range. Based on the obtained results, we discuss implications and misconceptions regarding barrier inhomogeneity, barrier height measurement, and reverse-bias temperature dependencies.

Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism.

Autism spectrum disorder (ASD) is characterized by impaired social communication and repetitive/stereotyped behaviors. The neuropeptide oxytocin (OXT) plays a critical role in regulating social behaviors in the central nervous system, as indicated in both human and animal studies. We hypothesized that central OXT deficit is one of causes of etiology of ASD, which may be responsible for the social impairments. To test our hypothesis, central OXT system was examined in valproic acid (VPA)-induced rat model of autism (VPA rat). Our results showed that adolescent VPA rats exhibited a lower level of OXT mRNA and fewer OXT-ir cells in the hypothalamus than control rats. Additionally, OXT concentration in cerebrospinal fluid (CSF) was reduced. The number of OXT-ir cells in the supraoptic nucleus (SON) of neonatal VPA rats was also lower. Autistic-like behaviors were observed in these animals as well. We found that an acute intranasal administration of exogenous OXT restored the social preference of adolescent VPA rats. Additionally, early postnatal OXT treatment had long-term effects ameliorating the social impairments and repetitive behaviors of VPA rats until adolescence. This was accompanied by an increase in OXT-ir cells. Taken together, we demonstrated there was central OXT deficiency in the VPA-induced rat model of autism, and showed evidence that early postnatal OXT treatment had a long-term therapeutic effect on the autistic-like behaviors in VPA rats.