Mouse nerve growth factor suppresses neuronal apoptosis in valproic acid-induced autism spectrum disorder rats by regulating the phosphoinositide-3-kinase/serine/threonine kinase signaling pathway.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restrictive behaviors. Mouse nerve growth factor (mNGF), a neurotrophic factor, is critical for neuronal growth and survival, and the mNGF treatment is considered a promising therapy for neurodegeneration. In light of this, we aimed to evaluate the effect of mNGF on neurological function in ASD. METHODS: An ASD rat model was established by intraperitoneal injection of valproic acid (VPA). Social behavior, learning, and memory of the rats were measured. TdT-mediated dUTP Nick-end labeling and Nissl assays were performed to detect neuronal apoptosis and survival in the hippocampus and prefrontal cortex. Apoptosis-related proteins and oxidative stress markers were detected. RESULTS: mNGF improved locomotor activity, exploratory behavior, social interaction, and spatial learning and memory in VPA-induced ASD rats. In the hippocampus and prefrontal cortex, mNGF suppressed neuronal apoptosis, increased the number of neurons, superoxide dismutase, and glutathione levels, and decreased reactive oxygen species, nitric oxide, TNF-α, and IL-1ß levels compared with the VPA group. In addition, mNGF increased the levels of Bcl-2, p-phosphoinositide-3-kinase (PI3K), and p-serine/threonine kinase (Akt), and decreased the levels of Bax and cleaved caspase-3, while the PI3K inhibitor LY294002 reversed these effects. CONCLUSION: These data suggest that mNGF suppressed neuronal apoptosis and ameliorated the abnormal behaviors in VPA-induced ASD rats, in part, by activating the PI3K/Akt signaling pathway.

GM1 Reduced the Symptoms of Autism Spectrum Disorder by Suppressing α-Syn Through Activating Autophagy.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that cannot be cured. The ASD rat model was developed in this study to demonstrate the role and mechanism of ganglioside GM1 (GM1). Rats were given valproic acid (VPA) to create the ASD rat model. The rats' behaviors were assessed using the Y-maze test, open-field test, three-chamber social interaction test, and Morris water maze test. Relative levels of glutathione (GSH), malondialdehyde (MDA), catalase (CAT), reactive oxygen species (ROS), and superoxide dismutase (SOD) were quantitated using relative kits. Nissl, TUNEL, immunofluorescent, and immunohistochemistry staining techniques were used. GM1 treatment improved the ASD model rats' behavior disorders, including locomotor activity and exploratory behavior, social interaction, learning and memory capacity, and repetitive behavior. Following GM1 injection, striatal neurons grew and apoptosis decreased. GM1 reduced the excessively elevated α-Syn in ASD by encouraging autophagy. The behavior disorder of ASD model rats was exacerbated by autophagy inhibition, which also increased α-Syn levels. By increasing autophagy, GM1 reduced α-Syn levels and, ultimately, improved behavioral abnormalities in ASD model rats.

A Meta-Analysis on the Impact of Prenatal and Early Childhood Antimicrobial Use on Autism Spectrum Disorders.

OBJECTIVE: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). DATA SOURCES: We searched PubMed and Embase databases for relevant studies from inception to August 2022. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD (P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal (P = 0.47 > 0.05) nor early childhood (P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. CONCLUSIONS: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.

Research on the Guiding Effect of CTCs on Postoperative Adjuvant Therapy for Patients with Early Stage Endometrial Cancer.

Endometrial tumor has increased in occurrence and fatality in China during the last 11 years, owing to inconsistent hormone use and modifications in people living surrounding and lifestyles. One of the three main gynaecological tumors is endometrial carcinoma (EC). Longer waiting duration of operation was linked to a lower chance of sustainability in endometrial tumor patients. Despite the great sustainability rate of endometrial tumor, only around 46 percent of patients undergo adjuvant treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and circulating free DNA (cfDNA) are the most investigated tumor noninvasive indicators. These circulating biomarkers are important in the knowledge of metastasis and tumorigenesis, and they could help researchers comprehend how cancer dynamics evolve throughout the therapy and illness development. In patients with solid tumor, the existence of circulating tumor cells (CTCs) in the peripheral blood is linked to a weak prognosis. However, there is a scarcity of information on how to detect CTCs in endometrial cancer (EC). Hence, in this paper, we analyze the guiding effect of CTCs on postoperative adjuvant treatment for sufferers with initial phase endometrial tumor using multi-cox regression method. The dataset is selected and the blood samples are collected using plasma separation method. The CTC is detected using differential diagnosis. The morphology and biological features, Immunocytochemistry, Genomic analysis, Transcriptomic analysis, Proteomic analysis, and molecular analysis are performed and the outcomes are evaluated.

TCHis mitigate oxidative stress and improve abnormal behavior in a prenatal valproic acid-exposed rat model of autism.

Troxerutin is known for its anti-inflammatory and antioxidative effects in nerve impairment. The purpose of this study is to investigate the effect of troxerutin and cerebroprotein hydrolysate injections (TCHis) on prenatal valproic acid (VPA)-exposed rats. The VPA was administered to pregnant rats on gestational day 12.5 to induce a model of autism. The offspring were given the treatment of TCHis on postnatal day (PND) 21-50. On PND 43-50, the behavioral analysis of offspring was performed after the treatment of TCHis for 1 h. On PND 50, the offspring were harvested and the brains were collected. The hippocampus and prefrontal cortex were isolated for relevant biochemical detections. The administration of TCHis increased pain sensitivity and improved abnormal social behaviors in prenatal VPA-exposed rats. Prenatal exposure of VPA induced neuronal loss and apoptosis, enhanced reactive oxygen species (ROS) production, and promoted oxidative stress in hippocampus and prefrontal cortex, whereas these effects were reversed by the postnatal treatment of TCHis. In addition, postnatal administration of TCHis ameliorated mitochondrial function in hippocampus and prefrontal cortex of prenatal VPA-exposed rats. This study concluded that postnatal treatment of TCHis reduced oxidative stress and ameliorated abnormal behavior in a prenatal VPA-induced rat model of autism.

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses.

OBJECTIVE: Emerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism. METHOD: Pregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28-48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44-48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured. RESULT: Electroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2. CONCLUSION: These data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

Acupuncture at ST36 Alleviates the Behavioral Disorder of Autistic Rats by Inhibiting TXNIP-Mediated Activation of NLRP3.

Autism is a common neurodevelopmental disorder that severely affects patients' quality of life. We aimed to investigate whether acupuncture at Zusanli (ST36) could alleviate the behavior disorder of autistic rats by inhibiting thioredoxin-interacting protein (TXNIP)-mediated activation of NLRP3. An autism model was induced by intraperitoneal injection of pregnant rats with valproic acid (VPA). The pups' behaviors were analyzed using hot plate, open field, Morris water maze, and 3-chamber social interaction tests. Nissl staining was used to visualize neurons in prefrontal cortex. Levels of TXNIP, NLRP3, interleukin (IL)-1ß, and caspase were determined by Western blot or quantitative real-time PCR. After ST36 acupuncture, pain sensitivity, autonomous activity, sociability index, sociability preference index, and learning and memory were improved in the autism model rats. Levels of TXNIP, NLRP3, IL-1ß, and caspase 1 were decreased after acupuncture. Interference with TXNIP alleviated the behavior disorders and inhibited NLRP3, caspase 1, and IL-1ß levels. In summary, ST36 acupuncture reduced TXNIP expression, inhibited the activation of the NLRP3 inflammasome, and alleviated the behavior disorder related to the prefrontal cortex of the autistic rats. These results point to a potential mechanism for acupuncture-induced improvement of autistic behavioral disorders.

Efficacy of Interventions Based on Applied Behavior Analysis for Autism Spectrum Disorder: A Meta-Analysis.

OBJECTIVE: To systematically evaluate evidence for the use of interventions based on appied behavior analysis (ABA) to manage various symptoms of children with autism spectrum disorder (ASD). METHODS: Sensitivity analyses were conducted by removing any outlying studies and subgroup analyses were performed to compare the effectiveness of ABA and early start denver model (ESDM), picture exchange communication systems (PECS) and discrete trial training (DTT). RESULTS: 14 randomized control trials of 555 participants were included in this meta-analysis. The overall standardized mean difference was d=-0.36 (95% CI -1.31, 0.58; Z=0.75, p=0.45) for autism general symptoms, d=0.11 (95% CI -0.31, 0.54; Z=0.52, p=0.60) for socialization, d=0.30 (95% CI -0.02, 0.61; Z=1.84, p=0.07) for communication and d=-3.52 (95% CI -6.31, -0.72; Z=2.47, p=0.01) for expressive language, d=-0.04 (95% CI -0.44, 0.36; Z=0.20, p=0.84) for receptive language. Those results suggested outcomes of socialization, communication and expressive language may be promising targets for ABA-based interventions involving children with ASD. However, significant effects for the outcomes of autism general symptoms, receptive language, adaptive behavior, daily living skills, IQ, verbal IQ, nenverbal IQ, restricted and repetitive behavior, motor and cognition were not observed. CONCLUSION: The small number of studies included in the present study limited the ability to make inferences when comparing ABA, ESDM, PECS and DTT interventions for children with ASD.

Rapid Preparation of Silsesquioxane-Based Ionic Liquids.

Three new hybrid ionic liquids (ILs) based on cage silsesquioxane (SQ) were rapidly prepared in high yields from octa(mercaptopropyl)silsesquioxane and 1-allyl-3-methylimidazolium salts (Br(-), BF4(-), PF6(-)) through the photochemical thiol-ene reaction. These SQ-based ILs exhibited low glass transition temperatures and good thermal stability. The unique amphiphilic nature of these hybrid ILs cause them to self-assemble into perfect vesicles with "yolk-shell" structures, in which cages formed the "yolk" due to their aggregation and outer anions formed the "shell".

A new titanosaurian sauropod from the Hekou Group (Lower Cretaceous) of the Lanzhou-Minhe Basin, Gansu Province, China.

Increased excavation of dinosaurs from China over the last two decades has enriched the record of Asian titanosauriform sauropods. However, the relationships of these sauropods remain contentious, and hinges on a few well-preserved taxa, such as Euhelopus zdanskyi. Here we describe a new sauropod, Yongjinglong datangi gen. nov. et sp. nov., from the Lower Cretaceous Hekou Group in the Lanzhou Basin of Gansu Province, northwestern China. Yongjinglong datangi is characterized by the following unique combination of characters, including seven autapomorphies: long-crowned, spoon-shaped premaxillary tooth; axially elongate parapophyses on the cervical vertebra; very deep lateral pneumatic foramina on the lateral surfaces of the cervical and cranial dorsal vertebral centra; low, unbifurcated neural spine fused with the postzygapophyses to form a cranially-pointing, triangular plate in a middle dorsal vertebra; an "XI"-shaped configuration of the laminae on the arches of the middle dorsal vertebrae; a very long scapular blade with straight cranial and caudal edges; and a tall, deep groove on the lateral surface of the distal shaft of the radius. The new specimen shares several features with other sauropods: a pronounced M. triceps longus tubercle on the scapula and ventrolaterally elongated parapophyses in its cervical vertebra as in Euhelopodidae. Based on phylogenetic analyses Yongjinglong datangi is highly derived within Titanosauria, which suggests either a remarkable convergence with more basal titanosauriform sauropods in the Early Cretaceous or a retention of plesiomorphic features that were lost in other titanosaurians. The morphology and remarkable length of the scapulocoracoid reveal an unusual relationship between the shoulder and the middle trunk: the scapulocoracoid spans over half of the length of the trunk. The medial, notch-shaped coracoid foramen and the partially fused scapulocoracoid synostosis suggest that the specimen is a subadult individual. This specimen sheds new light on the diversity of Early Cretaceous Titanosauriformes in China.

Hybrid thiol-ene network nanocomposites based on multi(meth)acrylate POSS.

First, multi(meth)acrylate functionalized POSS monomers were synthesized in this paper. Secondly, FTIR was used to evaluate the homopolymerization behaviors of multi(meth)acrylate POSS and their copolymerization behaviors in the thiol-ene reactions with octa(3-mercaptopropyl) POSS in the presence of photoinitiator. Results showed that the photopolymerization rate of multimethacrylate POSS was faster than that of multiacrylate POSS. The FTIR results also showed that the copolymerizations were dominant in the thiol-ene reactions with octa(3-mercaptopropyl) POSS, different from traditional (meth)acrylate-thiol system, in which homopolymerizations were predominant. Finally, the resulted hybrid networks based on POSS were characterized by XRD, FE-SEM, DSC, and TGA. The characterization results showed that hybrid networks based on POSS were homogeneous and exhibited high thermal stability.

Rational design and synthesis of hybrid porous polymers derived from polyhedral oligomeric silsesquioxanes via heck coupling reactions.

Heck coupling reactions are introduced as an efficient method to prepare porous polymers. Novel inorganic-organic hybrid porous polymers (HPPs) were constructed via Heck coupling reactions from cubic functional polyhedral oligomeric silsesquioxanes (POSS), iodinated octaphenylsilsesquioxanes (OPS) and octavinylsilsesquioxanes (OVS) using Pd(OAc)2 /PPh3 as the catalyst. Here, two iodinated OPS were used, IOPS and p-I8 OPS. IOPS was a mixture with 90% octasubstituted OPS (I8 ) and some nonasubstituted OPS (I9 ), while p-I8 OPS was a nearly pure compound with ≥99% I8 and ≥93% para-substitution. IOPS and p-I8 OPS reacted with OVS to produce the porous materials HPP-1 and HPP-2, which exhibited comparable specific surface areas with SBET of 418 ± 20 m(2) g(-1) and 382 ± 20 m(2) g(-1) , respectively, with total pore volumes of 0.28 ± 0.01 cm(3) g(-1) and 0.23 ± 0.01 cm(3) g(-1) , respectively. HPP-1 showed a broader pore size distribution and possessed a more significant contribution from the mesopores, when compared with HPP-2, thereby indicating that IOPS may induce more disorder because of the geometrical asymmetry. HPP-1 and HPP-2 possessed moderate carbon dioxide uptakes of 134 and 124 cm(3) g(-1) at 1 bar at 195 K, making them promising candidates for CO2 capture and storage. The synthesized porous polymers may be easily post-functionalized using the retained ethenylene groups.

[Effect of quantitative acupuncture manipulation on the skin temperature of acupoints].

OBJECTIVE: To verify the effect of lifting-thrusting reinforcing manipulation at Hegu (LI 4) of the right side on skin temperature on the Large Intestine Meridian. METHODS: Thirty healthy volunteers were needled at Hegu (LI 4) on the right side with lifting-thrusting reinforcing manipulation at the depth of 5 - 8 mm, 100 times/min in freqency for 1 min. With PowerLab 8/30 eight-channel high-speed recorders and specially equipped skin temperature detector, the temperatures of Shangyang (LI 1) on the bilateral side, Hegu (LI 4) and Kouheliao (LI 19) on the left side were tested at the time 30 min before the needling, 1 min during the needling and 30 min after the needling. RESULTS: After the lifting-thrusting reinforcing manipulation on the right Hegu (LI 4), the average skin temperature (27.89 +/- 3.56) degrees C before the needling at the left Hegu (LI 4) was increased to (28.30 +/- 2.81) degrees C, the temperature of right Shangyang (LI 1) (24.57 +/- 4.29) degrees C was increased to (26.30 +/- 4.32) degrees C, left Shangyang (LI 1) (25.13 +/- 5.07) degrees C to (26.58 +/- 4.92) degrees C and left Kouheliao (LI 19) (32.11 +/- 1.68) degrees C to (32.25 +/- 2.15) degrees C, all of which were significantly improved to different degrees (P < 0.01, P < 0.05). CONCLUSION: The lifting-thrusting reinforcing manipulation has an effect of increasing skin temperature of acupoints, and the temperature changes after needling are along meridians and have specificity of acupoins.

[Analysis on resistance testing and technological research of acupoints].

In order to summarize and analyze the progresses and problems of resistance testing and technology research on acupoints, investigate the related solutions, articles on resistance testing from 1990 to 2011 were collected, and advantages and shortcomings of different types of testing instruments were discussed in this article as well. Detection technology of acupoint impedance has under updating changes, which are often applied on locating acupoints and clinical diagnosis. The progresses of those technologies are mainly embodied in improvement of circuit model, which enable a longer testing duration, less media interference and so on. The previous studies often focus on resistance testing of the skin. Since dermal resistance does not equal to acupoint resistance, the designation of equivalent circuit does not embody the condition of cells, tissues and nerves at acupoints, and testing technology is often affected by factors such as polarization of electrodes, contact medium and anatomical characteristics of acupoints, the resistance of acupoints can not be taken as the effective framework of the diagnostic standard and judgement of therapeutic effect in clinic. Based on the key problems in resistance testing of acupoints, it is proposed by the article that the techniques and designation of circuit model should be reformed, and mathematical model should be established in the study to meet the requirement of the life system. Inductance of human body should be considered in resistance research of acupoints, and interference factors should be eliminate as far as possible in designation of equipments. Thus, the change law of acupoint resistance in the inner part of the body can be fully embodied by the designation of experiments.

[Hard and soft tissue changes following the treatment of Class II division 1 malocclusion using twin-block appliance].

OBJECTIVE: To investigate the hard and soft tissue changes following the treatment of Class II division 1 malocclusion using Twin-block appliance. METHODS: 50 Class II division 1 malocclusion subjects whose handwrist radiographs were in FG-G stage were selected. One group (27 patients) was treated with Twin-block appliance, the other group (23 patients) was observed without treatment The acquired data of cephalometric of two groups were analyzed statistically with SPSS 11.0. RESULTS: Soft tissue changes, Ls-E, Li-E, U1-Stms, Stms-Stmi, NsLs-FH, LsNsLi, LsNsPg', the angle of H decreased. Sn-Stms, Stmi-Me', Ns-Me', Sn-Me', NsLi-FH, NsPg'-FH, A'Ls-FH, B'Li-FH, LiB' Pg', CmSnLs, GSnPg', the angle of Z increased, there was statistically significant difference (P < 0.05). Hard tissue changes, SNB, L1-NB, IMPA increased, ANB, U1-SN, U1-NA, FMIA decreased, there was statistically significant difference (P < 0.05). CONCLUSION: Sagittal relationship between upper- and lower-jaws is effectively improved after orthopedics with Twin-block appliance. Lower face height increases. Soft tissue profile tends to be straight-styled.

[Soft tissue changes following the treatment of Class II division 1 malocclusion using Headgear-activator appliance].

PURPOSE: To investigate the soft tissue changes following the treatment of Class II division 1 malocclusion using Headgear-activator appliance. METHODS: Fifty Class II division 1 malocclusion subjects who were at peak high velocity on the growth curve were divided into two groups. Standardized lateral cephalogram was taken for each patient in the two groups before and after treatment. SPSS11.0 software package was used to calculate the mean and standard deviation, matched t-test was used to evaluate the changes of the soft tissues. RESULTS: The angle of CmSnLs,LiB'Pg' and Z increased, the angle of H, LsNsLi and LsNsPg' decreased, there was statistically significant difference between the two groups. CONCLUSIONS: Using Headgear-activator appliances, soft tissue profile is effectively improved. Soft tissue chin is moved forward obviously. Lip protrusion is decreased.