Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

Mutations that cause intellectual disability (ID) and autism spectrum disorder (ASD) are commonly found in genes that encode for synaptic proteins. However, it remains unclear how mutations that disrupt synapse function impact intellectual ability. In the SYNGAP1 mouse model of ID/ASD, we found that dendritic spine synapses develop prematurely during the early postnatal period. Premature spine maturation dramatically enhanced excitability in the developing hippocampus, which corresponded with the emergence of behavioral abnormalities. Inducing SYNGAP1 mutations after critical developmental windows closed had minimal impact on spine synapse function, whereas repairing these pathogenic mutations in adulthood did not improve behavior and cognition. These data demonstrate that SynGAP protein acts as a critical developmental repressor of neural excitability that promotes the development of life-long cognitive abilities. We propose that the pace of dendritic spine synapse maturation in early life is a critical determinant of normal intellectual development.

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report.

BACKGROUND: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. CASE PRESENTATION: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. CONCLUSIONS: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

High-Throughput Electrosynthesis of Gradient Polypyrrole Film Using a Single-Electrode Electrochemical System.

As an effective approach for materials synthesis, bipolar electrochemistry has been earning a renewed interest nowadays thanks to its unique features compared to conventional electrochemistry. Indeed, the wireless mode of electrode reactions and the generation of a gradient potential distribution above the bipolar electrode are among the most appealing qualities of bipolar electrochemistry. In particular, the gradient potential distribution is a highly attractive characteristic for the fabrication of surfaces with gradients in their chemical properties or molecular functionalities. Herein, we report the high-throughput electrosynthesis of gradient polypyrrole films by means of a new electrochemical cell design named the single-electrode electrochemical system (SEES). SEESs are made by attaching an inert plastic board with holes onto an indium tin oxide electrode, constructing multiple microelectrochemical cells on the same electrode. This type of arrangement enables parallel electrochemical reactions to be carried out simultaneously and controlled in a contactless manner by a single electrode. Several experimental conditions for polypyrrole film growth were extensively investigated. Furthermore, the gradient property of the polymer films was evaluated by thickness determination, surface morphology analysis, and contact angle measurements. The use of SEES has been demonstrated as a convenient and cost-effective strategy for high-throughput electrosynthesis and electroanalytical applications and has opened up a new door for gradient film preparation via a rapid condition screening process.

Generation of Oxygen Vacancies in Metal-Organic Framework-Derived One-Dimensional Ni0.4Fe2.6O4 Nanorice Heterojunctions for ppb-Level Diethylamine Gas Sensing.

Metal-organic frameworks (MOFs) are ideal sensing materials due to their distinctive morphologies, high surface area, and simple calcination to remove sacrificial MOF scaffolds. Oxygen vacancies (Ovs) can be efficiently generated by the thermal annealing of metal oxides in an inert atmosphere. Herein, MIL-53-based Fe and Fe/Ni-MOFs nanorices (NRs) were first prepared by using a solvothermal method, and then one-dimensional (1D) Fe2O3 and Ni0.4Fe2.6O4 NRs were derived from the MOFs after calcination at 350 °C in an air and argon (Ar) atmosphere, respectively. It was found that Ar-annealed Ni0.4Fe2.6O4 NRs have higher Ovs concentrations (82.11%) and smaller NRs (24.3 nm) than air-annealed NRs (65.68% & 31.5 nm). Beneficially, among the synthesized NRs, the Ar-Ni0.4Fe2.6O4 NRs show a higher sensitivity to diethylamine (DEA) (Ra/Rg = 23 @ 5 ppm, 175 °C), low detection limit (Ra/Rg = 1.2 @ 200 ppb), wide dynamic response (Ra/Rg = 93.5@ 30 ppm), high stability (30 days), and faster response/recovery time (4 s/38 s). Moreover, the 1D nanostructure containing heterostructures offers excellent sensing selectivity and a wide detection range from 200 ppb to 30 ppm in the presence of DEA. The outstanding gas sensing behavior can be attributable to synergistic impact, structural advantages, high concentration of Ovs, and the heterojunction interface, which can have profound effects on gas sensor performance. This study provides a unique technique for constructing high-performance gas sensors for ppb-level DEA detection and the formation of Ovs in metal oxides without the need for any additives.

In-bag extraction of tissue through an incision in the posterior vaginal wall in laparoscopic myomectomy: a large retrospective study.

BACKGROUND: Our purpose was to describe the outcomes of transvaginal in-bag tissue extraction tissue through an incision in the posterior vaginal wall the middle part incision of posterior vagina in laparoscopic myomectomy. METHODS: This was a retrospective study of patients who received laparoscopic myomectomy and in-bag tissue extraction through an incision in the posterior vaginal wall between January 2016 and December 2022. Patient characteristics, intra- and post-operative complications, and outcomes were collected and analyzed. RESULTS: A total of 511women were included in the analysis. The mean largest myoma diameter was 8.44 ± 3.56 cm; mean specimen weight was 789.23 ± 276.97 g; mean operative time was 129.01 ± 53.13minutes; and mean blood loss was 175.99 ± 210.96 mL. Within 30-days of surgery, no fever, infection, or vaginal bleeding was noted in any patient, and the vaginal incisions of all patients had healed well. There were no incisional hernias, pelvic infections, and vaginal adhesions noted at follow-up 3 months after the operation. There were 37 cases of vaginal delivery of the patients after surgery, and there were no lacerations of the posterior wall vaginal incision. CONCLUSIONS: Transvaginal in-bag extraction though an incision in the posterior vaginal wall is feasible and safe for removing tissue after laparoscopic myomectomy.

Machine learning prediction models for different stages of non-small cell lung cancer based on tongue and tumor marker: a pilot study.

OBJECTIVE: To analyze the tongue feature of NSCLC at different stages, as well as the correlation between tongue feature and tumor marker, and investigate the feasibility of establishing prediction models for NSCLC at different stages based on tongue feature and tumor marker. METHODS: Tongue images were collected from non-advanced NSCLC patients (n = 109) and advanced NSCLC patients (n = 110), analyzed the tongue images to obtain tongue feature, and analyzed the correlation between tongue feature and tumor marker in different stages of NSCLC. On this basis, six classifiers, decision tree, logistic regression, SVM, random forest, naive bayes, and neural network, were used to establish prediction models for different stages of NSCLC based on tongue feature and tumor marker. RESULTS: There were statistically significant differences in tongue feature between the non-advanced and advanced NSCLC groups. In the advanced NSCLC group, the number of indexes with statistically significant correlations between tongue feature and tumor marker was significantly higher than in the non-advanced NSCLC group, and the correlations were stronger. Support Vector Machine (SVM), decision tree, and logistic regression among the machine learning methods performed poorly in models with different stages of NSCLC. Neural network, random forest and naive bayes had better classification efficiency for the data set of tongue feature and tumor marker and baseline. The models' classification accuracies were 0.767 ± 0.081, 0.718 ± 0.062, and 0.688 ± 0.070, respectively, and the AUCs were 0.793 ± 0.086, 0.779 ± 0.075, and 0.771 ± 0.072, respectively. CONCLUSIONS: There were statistically significant differences in tongue feature between different stages of NSCLC, with advanced NSCLC tongue feature being more closely correlated with tumor marker. Due to the limited information, single data sources including baseline, tongue feature, and tumor marker cannot be used to identify the different stages of NSCLC in this pilot study. In addition to the logistic regression method, other machine learning methods, based on tumor marker and baseline data sets, can effectively improve the differential diagnosis efficiency of different stages of NSCLC by adding tongue image data, which requires further verification based on large sample studies in the future.

Oxygen Vacancies Induced by Pd Doping in Ni-P2O5/MoO3 Hollow Polyhedral Heterostructures for Highly Efficient Diethylamine Gas Sensing.

Semiconductor metal-oxide materials have a high surface-to-volume ratio and many active sites, making them potentially useful for gas sensing. Dopants introduced into the lattice can improve the catalytic activity of oxides and promote the formation of oxygen vacancies, hence improving the sensing performance of the materials. However, the simple preparation of materials with high sensitivity, selectivity, and a low detection limit remains a challenge. Herein, we report on the synthesis of Ni-P2O5/MoO3 and Pd-doped Ni-P2O5/MoO3 hollow polyhedral heterostructures (HPHSs) and their application in diethylamine (DEA) sensing for the first time. The Pd-doped Ni-P2O5/MoO3 HPHS was synthesized by doping different proportions of palladium-containing precursors using hydrothermal and solid-state reaction techniques. The concentration of oxygen vacancies in the HPHS composite increased by increasing Pd doping from 2 to 6 weight percent (wt %) but later reduced, according to X-ray photoelectron spectroscopy (XPS) measurements. Pd6%Ni-P2O5/MoO3 has the highest sensitivity to DEA (Ra/Rg = 42.5) and is 5.0 times and 42.5 times more sensitive than the pure Ni-P2O5/MoO3 HPHS (Ra/Rg = 8.5) and commercial ammonium phosphomolybdate (Ra/Rg = 1) at 175 °C toward 10 ppm DEA. Moreover, the DEA sensor exhibits a low detection limit (Ra/Rg = 3.5@1 ppm) with a wide dynamic response (Ra/Rg = 145.5@50 ppm). The remarkable improvement in DEA sensitivity is attributed to the hollow polyhedral structure, heterostructures, and oxygen vacancies formed by Pd doping. This study confirms that developing Pd-doped Ni-P2O5/MoO3 HPHSs provides an innovative approach for DEA sensors.

CCR2 downregulation attenuates spinal cord injury by suppressing inflammatory monocytes.

Specific elimination of blood-derived macrophages/monocytes following spinal cord injury (SCI) may suppress neurotoxicity without affecting the neuroprotective microglia at the injury sites. We aimed to deplete hematogenous monocytes by downregulating CCR2 through siCCR2-loaded nanoparticles and investigated its outcome in the recovery of locomotor function of SCI mice. We induced SCI in mice and examined the influx of blood-derived monocytes into the injury site. We constructed nanoparticles loaded with siRNA targeting CCR2 and examined its efficiency in downregulating the CCR2 expression in cultured RAW264.7 cells and monocytes in vivo. Finally, we assessed the effects of CCR2 downregulation in pro-inflammatory cytokine production, axon regeneration, and locomotor recovery of the SCI mice. We found that SCI significantly increased the CCL2 expression and number of blood-derived macrophages/monocytes in the lesion area. Nanoparticles loaded with siCCR2 significantly suppressed the CCR2 expression in hematogenous macrophages/monocytes, reduced the number of hematogenous macrophages/monocytes, and reduced pro-inflammatory cytokine production at the injury site. Finally, CCR2 downregulation promoted axon regeneration and improved locomotor recovery in SCI mice. Our study suggests that siCCR2 loading nanoparticles are efficient and specific in downregulating hematogenous macrophages/monocytes without affecting the neuroprotective microglia and its efficacy in promoting locomotor recovery in SCI mice warrants further investigation for its clinical application in SCI.

A tongue features fusion approach to predicting prediabetes and diabetes with machine learning.

BACKGROUND: Diabetics has become a serious public health burden in China. Multiple complications appear with the progression of diabetics pose a serious threat to the quality of human life and health. We can prevent the progression of prediabetics to diabetics and delay the progression to diabetics by early identification of diabetics and prediabetics and timely intervention, which have positive significance for improving public health. OBJECTIVE: Using machine learning techniques, we establish the noninvasive diabetics risk prediction model based on tongue features fusion and predict the risk of prediabetics and diabetics. METHODS: Applying the type TFDA-1 Tongue Diagnosis Instrument, we collect tongue images, extract tongue features including color and texture features using TDAS, and extract the advanced tongue features with ResNet-50, achieve the fusion of the two features with GA_XGBT, finally establish the noninvasive diabetics risk prediction model and evaluate the performance of testing effectiveness. RESULTS: Cross-validation suggests the best performance of GA_XGBT model with fusion features, whose average CA is 0.821, the average AUROC is 0.924, the average AUPRC is 0.856, the average Precision is 0.834, the average Recall is 0.822, the average F1-score is 0.813. Test set suggests the best testing performance of GA_XGBT model, whose average CA is 0.81, the average AUROC is 0.918, the average AUPRC is 0.839, the average Precision is 0.821, the average Recall is 0.81, the average F1-score is 0.796. When we test prediabetics with GA_XGBT model, we find that the AUROC is 0.914, the Precision is 0.69, the Recall is 0.952, the F1-score is 0.8. When we test diabetics with GA_XGBT model, we find that the AUROC is 0.984, the Precision is 0.929, the Recall is 0.951, the F1-score is 0.94. CONCLUSIONS: Based on tongue features, the study uses classical machine learning algorithm and deep learning algorithm to maximum the respective advantages. We combine the prior knowledge and potential features together, establish the noninvasive diabetics risk prediction model with features fusion algorithm, and detect prediabetics and diabetics noninvasively. Our study presents a feasible method for establishing the association between diabetics and the tongue image information and prove that tongue image information is a potential marker which facilitates effective early diagnosis of prediabetics and diabetics.

Evaluation of renewable pH-responsive starch-based flocculant on treating and recycling of highly saline textile effluents.

Herein, we report a novel renewable pH-responsive starch-based flocculant (CIAT-ST) via etherifying 2-chloro-4,6-isopropylamino-[1,3,5]-triazine (CIAT) onto the starch backbones for decontamination and reuse of highly saline effluents. The obtained CIAT-ST shows a unique pH-sensibility and reversibility in response to a subtle pH change due to a pH-controllable surface charge density of polymer chains. The level of residual CIAT-ST in the solution can be facilely monitored by using UV-vis detection. The dye flocculation performance of CIAT-ST was evaluated by using a batch experiment. The results exhibited that the dye removal was highly dependent on the solution pH (optimal pH was 2), the flocculation equilibrium can be achieved within 5 min, and the maximum flocculation capacity of CIAT-ST for K-2BP and KN-B5 were calculated to be 2452.6 ± 23.9 and 792.7 ± 14.1 mg/g, respectively. The multiple flocculation mechanisms, including charge neutralization, bridging and charge patching, may participate in the flocculation process. Adjustment in pH-mediated hydrophilicity-hydrophobicity switch of flocculant facilitates readily recovery and then sequentially reused three times while retaining satisfying flocculation efficiency. A significant contribution was also confirmed that the highly saline effluents after flocculation and sedimentation were reused in three successive dyeing processes without sacrificing fabric quality (ΔE* < 1) due to relatively low polymer residuals, and the efficiency of salt reuse for consecutive regeneration processes could be achieved above 85%. The present work could provide alternative thoughts for the reutilization of spent flocculant and clarified saline wastewater, which is also an efficient and sustainable strategy for textile wastewater management.

Clinical data mining on network of symptom and index and correlation of tongue-pulse data in fatigue population.

BACKGROUND: Fatigue is a kind of non-specific symptom, which occurs widely in sub-health and various diseases. It is closely related to people's physical and mental health. Due to the lack of objective diagnostic criteria, it is often neglected in clinical diagnosis, especially in the early stage of disease. Many clinical practices and researches have shown that tongue and pulse conditions reflect the body's overall state. Establishing an objective evaluation method for diagnosing disease fatigue and non-disease fatigue by combining clinical symptom, index, and tongue and pulse data is of great significance for clinical treatment timely and effectively. METHODS: In this study, 2632 physical examination population were divided into healthy controls, sub-health fatigue group, and disease fatigue group. Complex network technology was used to screen out core symptoms and Western medicine indexes of sub-health fatigue and disease fatigue population. Pajek software was used to construct core symptom/index network and core symptom-index combined network. Simultaneously, canonical correlation analysis was used to analyze the objective tongue and pulse data between the two groups of fatigue population and analyze the distribution of tongue and pulse data. RESULTS: Some similarities were found in the core symptoms of sub-health fatigue and disease fatigue population, but with different node importance. The node-importance difference indicated that the diagnostic contribution rate of the same symptom to the two groups was different. The canonical correlation coefficient of tongue and pulse data in the disease fatigue group was 0.42 (P < 0.05), on the contrast, correlation analysis of tongue and pulse in the sub-health fatigue group showed no statistical significance. CONCLUSIONS: The complex network technology was suitable for correlation analysis of symptoms and indexes in fatigue population, and tongue and pulse data had a certain diagnostic contribution to the classification of fatigue population.

A retrospective study to compare the treatment outcomes with and without surgical navigation for fracture of the orbital wall.

PURPOSE: To evaluate the outcomes with and without aid of a computer-assisted surgical navigation system (CASNS) for treatment of unilateral orbital wall fracture (OWF). METHODS: Patients who came to our hospital for repairing unilateral traumatic OWF from 2014 to 2017 were included in this study. The patients were divided into the navigation group who accepted orbital wall reconstruction aided by CASNS and the conventional group. We evaluated the surgical precision in the navigation group by analyzing the difference between actual postoperative computed tomography data and preoperative virtual surgical plan through color order ratios. We also compared the duration of surgery, enophthalmos correction, restoration of orbital volumes, and improvement of clinical symptoms in both groups systemically. Quantitative data were presented as mean ± SD. Significance was determined by the two-sample t-test using SPSS Version 19.0 A p < 0.05 was considered statistically significant. RESULTS: Seventy patients with unilateral OWF were included in the study cohort. The mean difference between preoperative virtual planning and actual reconstruction outcome was (0.869 ± 0.472) mm, which means the reconstruction result could match the navigation planning accurately. The mean duration of surgery in the navigation group was shorter than it is in the control group, but not significantly. Discrepancies between the reconstructed and unaffected orbital-cavity volume and eyeball projection in the navigation group were significantly less than that in the conventional group. One patient had remnant diplopia and two patients had enophthalmos after surgery in the navigation group; two patients had postoperative diplopia and four patients had postoperative enophthalmos in the conventional group. CONCLUSION: Compare with the conventional treatment for OWF, the use of CASNS can provide a significantly better surgical precision, greater improvements in orbital-cavity volume and eyeball projection, and better clinical results, without increasing the duration of surgery.

A Security-Enhanced Image Communication Scheme Using Cellular Neural Network.

In the current network and big data environment, the secure transmission of digital images is facing huge challenges. The use of some methodologies in artificial intelligence to enhance its security is extremely cutting-edge and also a development trend. To this end, this paper proposes a security-enhanced image communication scheme based on cellular neural network (CNN) under cryptanalysis. First, the complex characteristics of CNN are used to create pseudorandom sequences for image encryption. Then, a plain image is sequentially confused, permuted and diffused to get the cipher image by these CNN-based sequences. Based on cryptanalysis theory, a security-enhanced algorithm structure and relevant steps are detailed. Theoretical analysis and experimental results both demonstrate its safety performance. Moreover, the structure of image cipher can effectively resist various common attacks in cryptography. Therefore, the image communication scheme based on CNN proposed in this paper is a competitive security technology method.

Mineralized Supramolecular Hydrogels Bearing Tunable Thermo-Responsiveness.

Although a variety of biomimetic mineralized materials have been created in the lab, the vast majority of these manmade examples lack response to external stimuli. Here, mineralized supramolecular hydrogels with on-demand thermo-responsiveness that are formed by a simple, physical crosslinking between amorphous CaCO3 (ACC) nanoparticles and poly(acrylic acid) (PAA) are reported. Upon the addition of Na2 CO3 solution into a mixture composed of PAA and CaCl2 , amorphous ACC nanoparticles are formed in situ and simultaneously crosslinked by PAA chains, giving rise to the mineralized hydrogels. Interestingly, upon tuning the content of the formed ACC, hydrogels with different types of thermo-responsiveness can be easily obtained, and the transparencies of the resulting hydrogels are dramatically changed during the temperature-driven phase transitions. As an application, these thermo-responsive mineralized hydrogels are used to control the exposure of UV light, which is successfully applied to switch fluorescent signals in response to temperature.

Inequities in consistent condom use among sexually experienced undergraduates in mainland China: implications for planning interventions.

BACKGROUND: Since pre-exposure prophylaxis (PrEP) is mainly prescribed to high-risk uninfected individuals, consistent condom use (CCU) continues to be recommended as an inexpensive, feasible, practical and acceptable way to prevent the general population from acquiring and transmitting HIV through sexual intercourse. The objective of this cross-sectional study was to compare the relative importance of various determinants of CCU among sexually experienced undergraduates in mainland China so as to assess and subsequently to suggest ways to eliminate inequities in its use. METHOD: From September 10, 2018, to January 9, 2019, an anonymous self-administered online questionnaire was voluntarily completed by 12,750 participants distributed across 30 provinces in mainland China (except for Tibet). The present analysis was restricted to 2054 sexually experienced undergraduates. Pearson's chi-square test and Logistic regression models were chosen to analyze the factors associated with CCU. RESULTS: The overall rate of CCU was 61.3% [95% confidence interval (CI) = 59.2-63.4%]. CCU was inequitably distributed since enabling factors exerted greater effects than predisposing and need variables. Compared with heterosexual men, heterosexual women [adjusted odds ratio (AOR) = 0.78, 95% confidence interval (CI):0.64-0.96)], non-heterosexuals men (AOR = 0.64, 95% CI:0.45-0.92) and women (AOR = 0.68, 95% CI:0.47-0.99) were less prone to using condoms consistently. Those with more resources [i.e., higher levels of self- efficacy for condom use (AOR = 2.86, 95% CI:2.35-3.49) and being knowledgeable of the national AIDS policy (AOR = 1.50, 95% CI:1.23-1.82)], and those with lower need for condoms [i.e., late initiation of sexual activity (AOR = 1.34, 95% CI:1.09-1.64) and single sexual partner (AOR = 1.68,95% CI:1.21-2.33)] were more likely to be consistent condom users. CONCLUSIONS: In order to increase consistency of condom use and simultaneously reduce the remaining inequities, a comprehensive intervention measure should be taken to target heterosexual women, non-heterosexual men and women, and those with higher need for condoms, improve their condom use self- efficacy and raise their awareness of the national AIDS policy.

[Genetic diagnosis and non-invasive prenatal testing of a fetus with Prader-Willi/Angelman syndrome].

OBJECTIVE: To explore the genetic basis for a fetus featuring growth restriction and validate the effectiveness of a novel noninvasive prenatal testing (NIPT) technique for the detection of chromosomal microdeletions. METHODS: Next-generation sequencing(NGS) and fluorescence in situ hybridization(FISH) were used to analyze the DNA of the fetus. Conventional G-banding was used to analyze the karyotypes of the fetus and its parents. High-throughput sequencing was used to analyze free fetal DNA. RESULTS: NGS analysis has revealed a 4.88 Mb deletion at 15q11.2-q13.1 region in the fetus, which has a 99% overlap with the critical region of Prader-Willi syndrome (Type 2) and Angelman syndrome (Type 2) and encompassed critical genes including SNRPN and UBE3A. NIPT also revealed a 4.6 Mb deletion at 15q12, which was consistent with the results of fetal cord blood and amniotic DNA testing. FISH assay has confirmed the result of NGS. By karyotying, all subjects showed a normal karyotypes at a level of 320~400 bands. CONCLUSION: It is quite necessary to carry out genetic testing on fetuses showing growth restriction. NIPT for fetal chromosomal microdeletions/microduplication syndromes is highly accurate for the diagnosis of Prader-Willi/Angelman syndrome.

The prevalence of and factors associated with willingness to utilize HTC service among college students in China.

BACKGROUND: College students in China are emerging as one of the most vulnerable groups to contract HIV, because they are in a sexually active age group and also because of their open attitude toward sex and high risk sexual behaviors. This study aimed to explore the prevalence of willingness among college students to utilize HIV testing and counseling (HTC) service and the factors that may affect willingness, including predisposing, enabling and need factors, based on the Andersen's behavioral model. METHODS: A cross-sectional study was conducted from October 6, 2016 to December 31, 2016 in Hubei University of Science and Technology in China. After signing informed consent, college students completed a self-designed online questionnaire distributed via  https://www.wjx.cn/ voluntarily, anonymously and confidentially. Pearson's chi-square test and Logistic regression models were chosen to analyze the factors associated with willingness to utilize HTC service. RESULTS: Out of 3314 college students in the sample, 2583 (77.9%) expressed their willingness to utilize HTC service. After adjustment, those with low levels of discrimination towards people living with HIV (PLHIV) (OR = 1.41, 95%CI:1.17-1.68), being more knowledgeable about free HTC service centers (OR = 1.44, 95%CI:1.17-1.77), having recognized the necessity to provide HTC service in the local university (OR = 2.20, 95%CI:1.73-2.80), and having a higher HIV risk perception (OR = 1.64, 95%CI:1.37-1.95) were more willing to utilize HTC service, compared with their respective counterparts. CONCLUSIONS: In order to improve their willingness to utilize HTC service and finally to achieve the goal of zero-AIDS, a comprehensive intervention measure should be taken to publicize HTC service, eliminate stigma and discrimination against PLHIV, recruit and train peer volunteers to serve in the local university, and increase self-perceived risk of HIV infection.

Assessing the Quality of Life in Patients With Dentofacial Deformities Before and After Orthognathic Surgery.

PURPOSE: This study aimed to assess the effect of health-related quality of life (QoL) among patients with dentofacial deformities who underwent orthognathic surgery compared with a control group without dentofacial deformities by use of generic oral health and condition-specific approaches. PATIENTS AND METHODS: In this prospective study, 2 questionnaires were administered to 85 patients (31 male and 54 female patients) who were evaluated before undergoing orthognathic surgery. The Short Form Oral Health Impact Profile Questionnaire (OHIP-14) and the Orthognathic Quality of Life Questionnaire (OQLQ) were administered before and 5 to 7 months after orthognathic surgery. The control group comprised 96 young university student volunteers without dentofacial deformities. RESULTS: The questionnaires were collected 5 to 7 months after surgery. The preoperative scores of the patients and the control group were contrasted separately. The respondents' postoperative OHIP-14 and OQLQ scores were significantly lower (P < .001 for total scores). The preoperative OQLQ scores for all domains were significantly higher among the patients than among the controls (P < .001 for total scores), whereas the total scores and 3 subscale scores of the OHIP-14 in the functional and psychological domains were significantly higher among the patients than among the controls (P < .05 for total scores). The preoperative and postoperative OQLQ total scores were remarkably different between male and female patients (P < .05). The postoperative OQLQ total scores were considerably higher in older patients than in younger patients (P < .05). All patients in the Class III group who underwent double-jaw surgery showed remarkable changes after surgery (P < .001 for total scores). CONCLUSIONS: Patients with dentofacial deformities had a poorer QoL compared with the healthy population, especially in functional and psychological aspects. Orthognathic surgery had a significant positive impact on QoL. Patients with Class III malocclusion who underwent double-jaw surgery seemingly benefitted the most after surgery.

The USP7 Inhibitor P5091 Induces Cell Death in Ovarian Cancers with Different P53 Status.

BACKGROUND/AIMS: Ovarian cancer is often diagnosed at later stages with poor prognosis. Recent studies have associated the expression of deubiquitylase USP7 with the survival of ovarian cancers. Being a cysteine protease, USP7 could become a target for pharmacological intervention. Therefore, in this study, we assessed the influence of its inhibitor P5091 on ovarian cancer cells. METHODS: Ovarian cancer cells were treated with P5091, and cell proliferation was measured with MTT assay; cell morphology was inspected under a phase-contrast microscope; cell cycle and cell death were examined by flow cytometry. To gain mechanistic insights into its effects, immunoblotting was performed to detect USP7, HDM2, p53, p21, apoptosis and autophagy related proteins. RESULTS: P5091 effectively suppressed the growth of ovarian cancer cells, caused cell cycle blockage, and induced necrosis and apoptosis with more severe phenotypes observed in HeyA8 cells with wild-type p53 than in OVCAR-8 cells with mutant p53. P5091 also prompted autophagy, with more efficient p62 degradation in HeyA8. CONCLUSION: P5091 shows efficacy in suppressing ovarian cancers harbouring wild-type and mutant p53. Its effects seemed to be enhanced by wild-type p53. The potency of this USP7 inhibitor also correlated with autophagy to some extent. Therefore, the pharmacological targeting of USP7 may serve as a potential therapeutic strategy and warrants further investigation.

Primary visual cortex shows laminar-specific and balanced circuit organization of excitatory and inhibitory synaptic connectivity.

KEY POINTS: Using functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory neurons in layers 2/3-6 of the mouse visual cortex (V1). Laminar-specific synaptic wiring diagrams of excitatory neurons were constructed on the basis of circuit mapping. The present study reveals that that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks in V1. ABSTRACT: In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3-6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer-specific organization of excitatory inputs. Remarkably, the spatial extent of inhibitory inputs of excitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex.