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AIM: To assess the possibility of using different large language models (LLMs) in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases: ChatGPT-4, ChatGPT-3.5, Claude 2, PaLM2, and SenseNova. METHODS: A group of experienced ophthalmology professors were asked to develop a 100-question single-choice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions. The exam includes questions on the following topics: keratitis disease (20 questions), keratoconus, keratomalaciac, corneal dystrophy, corneal degeneration, erosive corneal ulcers, and corneal lesions associated with systemic diseases (20 questions), conjunctivitis disease (20 questions), trachoma, pterygoid and conjunctival tumor diseases (20 questions), and dry eye disease (20 questions). Then the total score of each LLMs and compared their mean score, mean correlation, variance, and confidence were calculated. RESULTS: GPT-4 exhibited the highest performance in terms of LLMs. Comparing the average scores of the LLMs group with the four human groups, chief physician, attending physician, regular trainee, and graduate student, it was found that except for ChatGPT-4, the total score of the rest of the LLMs is lower than that of the graduate student group, which had the lowest score in the human group. Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers, giving very little chance of an incorrect answer. ChatGPT-4 showed higher credibility when answering questions, with a success rate of 59%, but gave the wrong answer to the question 28% of the time. CONCLUSION: GPT-4 model exhibits excellent performance in both answer relevance and confidence. PaLM2 shows a positive correlation (up to 0.8) in terms of answer accuracy during the exam. In terms of answer confidence, PaLM2 is second only to GPT4 and surpasses Claude 2, SenseNova, and GPT-3.5. Despite the fact that ocular surface disease is a highly specialized discipline, GPT-4 still exhibits superior performance, suggesting that its potential and ability to be applied in this field is enormous, perhaps with the potential to be a valuable resource for medical students and clinicians in the future.

Objective To examine the levels of systemic inflammatory response index (SIRI) and serum lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with acute carbon monoxide poisoning (ACOP), and to explore the predictive value of SIRI, Lp - PLA2 and their combination for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods Total 265 patients with ACOP diagnosed and treated in Harrison International Peace Hospital of Hebei Medical University, The Second People's Hospital of Hengshui and The No.4 People's Hospital of Hengshui from March 2020 to March 2023 were included. SIRI and serum Lp-PLA2 levels were measured. According to the occurrence of DEACMP, they were divided into DEACMP group (n = 32) and non -DEACMP group (n = 233), while according to the degree of poisoning, they were divided into mild poisoning group (n = 20), moderate poisoning group (n = 107) and severe poisoning group (n = 138). Univariate and multivariate Logistic regression analyses were used to screen the risk factors of DEACMP in patients with ACOP, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive efficacy of SIRI, Lp - PLA2 and their combination for DEACMP. Results The levels of SIRI (t = 13.068, P = 0.000) and serum Lp-PLA2 (t = 8.208, P = 0.000) in DEACMP group were higher than those in non-DEACMP group, and their levels gradually increased with the severity of poisoning, the levels of SIRI (t = 8.764, P = 0.000; t = 4.586, P = 0.000) and Lp-PLA2 (t = 3.726, P = 0.000; t = 2.038, P = 0.044) in the severe poisoning group and moderate poisoning group were higher than those in the mild poisoning group, and the levels of SIRI and serum Lp-PLA2 in the severe poisoning group were also higher than those in the moderate poisoning group (t = 10.294, P = 0.000; t = 2.700, P = 0.007). Logistic regression analysis showed the severe poisoning (OR = 11.695, 95%CI: 4.893-39.994; P = 0.000), SIRI increased (OR = 1.600, 95%CI: 1.033-2.476; P = 0.001) and Lp - PLA2 increased (OR = 11.302, 95%CI: 1.486-38.933; P = 0.000) were risk factors of DEACMP in patients with ACOP. ROC curve showed that area under the curve (AUC) predicted by Lp-PLA2, SIRI and their combination were 0.82 (95%CI: 0.754-0.894, P = 0.000), 0.82 (95%CI: 0.739-0.895, P = 0.000) and 0.87 (95%CI: 0.805-0.934, P = 0.000), sensitivity were 0.66, 0.72 and 0.84, specificity were 0.85, 0.88 and 0.90, respectively. The prediction efficiency of Lp-PLA2 combined with SIRI was better than that of Lp- PLA2 (t = 2.198, P = 0.027) or SIRI (t = 2.268, P = 0.023) alone. Conclusions DEACMP is easy to occur when SIRI and serum Lp-PLA2 were high in patients with ACOP. The combined detection of Lp-PLA2 and SIRI can be used for early screening of DEACMP.

Due to cylinder friction, valve dead zone effect, flow nonlinearity, and measurement noise exist in pneumatic system. In the actual machining, it is difficult to achieve precise control of the pneumatic servo polishing system using the traditional PID algorithm, so the machining accuracy of the blades cannot be guaranteed. A sliding mode control (SMC) method based on high gain observer (HGO) is proposed. The HGO observes the output signal of the system and feeds the estimated signal back to the SMC to ensure that the observation error is uniform ultimate boundedness. Simulation and experiments show that compared with the PID algorithm, the steady-state error of HGO-SMC can be reduced by 66.4%. Compared with SMC(sgn), the high-frequency chattering of HGO-SMC can be reduced by 72.5%. Moreover, the polishing processing experiment shows that HGO-SMC can improve the form and position accuracy by 52.6% and reduce the surface roughness by 55.6%, compared with the original PID control algorithm of the polishing machine tool.

Abstract Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.

Abstract Background We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. Methods We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. Results Children with ASD had a shorter breastfeeding duration in infancy (8 (3–12) months vs. 10 (6–14) months, P

Abstract Genetic heterogeneity poses a challenge to research and clinical translation of autism spectrum disorder (ASD). In this study, we conducted a plasma proteomic and metabolomic study of children with ASD with and without risk genes (de novo mutation) and controls to explore the impact of genetic heterogeneity on the search for biomarkers for ASD. In terms of the proteomic and metabolomic profiles, the groups of children with ASD carrying and those not carrying de novo mutation tended to cluster and overlap, and integrating them yielded differentially expressed proteins and differential metabolites that effectively distinguished ASD from controls. The mechanisms associated with them focus on several common and previously reported mechanisms. Proteomics results highlight the role of complement, inflammation and immunity, and cell adhesion. The main pathways of metabolic perturbations include amino acid, vitamin, glycerophospholipid, tryptophan, and glutamates metabolic pathways and solute carriers‐related pathways. Integrating the two omics analyses revealed that L‐glutamic acid and malate dehydrogenase may play key roles in the pathogenesis of ASD. These results suggest that children with ASD may have important underlying common mechanisms. They are not only potential therapeutic targets for ASD but also important contributors to the study of biomarkers for the disease.

Polishing force is one of the key process parameters in the polishing process of blisk blades, and its control accuracy will affect the surface quality and processing accuracy of the workpiece. The contact mechanism between the polishing surface and flap wheel was analyzed, and the calculation model of the polishing force and nonlinear dynamic model of the polishing force control system was established. Considering the influence of friction characteristics, parameter perturbation, and nonlinear dead zone on the control accuracy of the polishing force system, an adaptive fuzzy sliding mode controller (AFSMC) was designed. AFSMC uses a fuzzy system to adaptively approximate the nonlinear function terms in the sliding mode control law, adopts an exponential approach law in the switching control part of the sliding mode control (SMC), and designs the adaptive law for adjustable parameters in the fuzzy system based on the Lyapunov Theorem. Simulation and experimental results show that the designed AFSMC has a fast dynamic response, strong anti-interference ability, and high control accuracy, and it can reduce SMC high-frequency chatter. Polishing experiments show that compared with traditional PID, AFSMC can improve the form and position accuracy of the blade by 42% and reduce the surface roughness by 50%.

Abstract Background Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. Methods We enrolled 1019 ASD preschoolers aged 2–7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. Results Based on general developmental quotient (GQ) 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55–69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. Conclusions Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. Trial registration ChiCTR2000031194 , registered on 03/23/2020.

Objective To investigate the effect of NAIF1 in gastric cancer cell lines MKN45. Methods We constructed pLVX-Tight-Flag-NAIF1-puro plasmid with Tet-on system. DOX was added to induce NAIF1 expression in MKN45 cells. The cells were collected at 0, 6, 12 and 24 hours after DOX addition for gene expression microarray detection and biological analysis of differentially expressed genes. qRT-PCR and Western blot were used to verify the changes in mRNA and protein levels of the selected target differential genes. Results The biological analysis of gene microarray hybridization results showed that IFIT1, IFIT2 and IFIT3 expression significantly increased at 24h, qRT-PCR also showed this change, and Western blot further verified the change in protein level. However, IFIT5 showed no significant change in mRNA and gene expression. Conclusion Over-expression of NAIF1 in gastric cancer cells can promote the expression of some immune system-related IFIT family proteins.

Background: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. Objective: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. Methods: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. Results: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted β = 0.277, P

Background: Different Traditional Chinese Medicine (TCM) in the format of granules, such as Kanggan Granules (KangGs), Kouyanqing Granules (KouGs), Lianhua Qingwen Granules (LQGs), Qingkailing Granules (QGs) and Xiao'er Qingjie Granules (XQJGs), collectively named Yinhua-based herbal granules (YH-HGs) have been widely used in the management of pediatric outpatients with herpangina. Few head-to-head randomized controlled trials (RCTs) have compared the efficacy of these agents. This network meta-analysis (NMA) was conducted to indirectly compare the efficacy of YH-HGs. Methods: This systematic review and fixed-effect NMA was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for NMA. RCTs assessing the efficacy and safety of YH-HGs in children that were also receiving ribavirin as the conventional therapy were searched from eight databases and two trial registers up to Jan 13, 2022. The primary outcome was total effectiveness rate (TER). The secondary outcomes were total adverse events (TAEs) and the time to symptom improvement of fever, vesicles, pain and salivation. Relative risk (RR) and weighted mean difference with 95% confidence intervals (CIs) were estimated by direct pairwise meta-analysis (MA) and NMA. Results: A total of 10 RCTs, enrolling 1 017 pediatric patients, were included. YH-HGs were better than no medication (NM) in TER (RR = 1.22, 95%CIs, 1.16 – 1.28) by direct pairwise MA, in which KangGs (RR = 1.24, 95%CIs, 1.05 – 1.47), KouGs (RR = 1.17, 95%CIs, 1.08 – 1.27), LQGs (RR = 1.24, 95%CIs, 1.14 – 1.35), QGs (RR = 1.33, 95%CIs, 1.11 – 1.58) and XQJGs (RR = 1.18, 95%CIs, 1.00 – 1.40) were also more efficient than NM. As for secondary outcomes, YH-HGs was associated with a 103% increased risk of TAEs compared to NM, but no significant differences were found. YH-HGs has a more positive symptom improvement effect than NM in fever, vesicles, pain and salivation. The ranking results showed that QGs (79.2%) had the highest probability ranking first in TER and KangGs (63.6%) ranked as the second, followed by LQGs (52.4%), XQJGs (50.3%), KouGs (49.7%), and NM (4.9%) at last. Conclusions: Our findings support the better efficacy of YH-HGs than NM as regards TER. QGs, KangGs, LQGs, XQJGs, KouGs remain superior to NM and their clinical choice should depend on the patient's conditions to improve symptoms better for the different effects. Given the limitations of NMA, head-to-head RCTs with high-quality are needed.

Abstract Background High prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels. Methods Using a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children’ s sleep habits questionnaire (CSHQ) assessed sleep conditions. Results The prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%, p

The stability and high productivity of heterogeneous terpenoid production in Escherichia coli expression system is one of the most key issues for its large scale industrialization. In the current study on taking lycopene biosynthesis as an example, an integrated Escherichia coli system has been generated successfully, which resulted into stable and high lycopene production. In this process, two modules of mevalonate (MVA) pathway and one module of lycopene expression pathway were completely integrated in the chromosome. Firstly, the copy number and integrated position of three modules of heterologous pathways were rationally optimized. Later, a strain DH416 equipped with heterogeneous expression pathways through chromosomal integration was efficiently derived from parental strain DH411. The evolving DH416 strain efficiently produced the lycopene level of 1.22 g/L (49.9 mg/g DCW) in a 5 L fermenter with mean productivity of 61.0 mg/L/h. Additionally, the integrated strain showed more genetic stability than the plasmid systems after successive 21st passage.

PurposeTo evaluate the performance of TB-LAMP in the diagnosis of TB empyema using pleural tissue specimens obtained during pleural decortication.MethodsUsing the clinical records and the different diagnostic test results of patients who underwent pleural decortication in a TB-designated hospital over 3.5 years, we calculated the sensitivity, specificity positive predictive, and negative predictive values of the pathology, MGIT 960 culture, and TB-LAMP obtained by using pleural tissue specimens against the etiologic diagnosis and composite clinical reference standard (CCRS) as the reference standards.ResultA total of 304 patients' records were extracted. All these patients had gone through pleural decortication. When the etiologic diagnosis was used as the reference, the sensitivity of TB-LAMP in identifying TB empyema was 77.8% (compared to 10.6% of MGIT 960 P < 0.05). The sensitivity of MGIT 960, pathology, and TB-LAMP was 8.2%, 77.7%, and 67.2% against CCRS as the reference; and the specificity of the three was 100.0, 100.0, and 96.2% against the same standard. A combination of pathology and TB-LAMP would increase the sensitivity and specificity to 84.7 and 96.0%. Using TB-LAMP to diagnose TB empyema using pleural tissue samples obtained from pleural decortication was faster with satisfactory performance.ConclusionTB-LAMP has great potential in faster and more accurate diagnosis of TB empyema. Our findings provide insights for optimizing diagnostic algorithms for TB empyema.

This study aims at developing a framework for assessing and tracking structural conditions by combining computer vision-based three-dimensional (3D) reconstruction and vibration measurement. Starting from a finite element (FE) model with unknown geometric and material properties, the framework seeks to obtain the accurate representation of the structure by applying a sequence of two types of operations: (1) image collection, 3D reconstruction, and the extraction of localized geometric properties, and (2) vibration measurement, operational modal analysis, and extraction of global stiffness properties. The first step, termed the computer vision step, is based on the alignment of the approximate initial finite element model to the 3D reconstruction, from which the area and second moment of area associated with each element of the model are retrieved by slicing the reconstructed mesh. The second step, termed the vibration measurement step, performs system identification using vibration measurement data, followed by the Bayesian model updating to calibrate the element stiffness. Every time one of those operations is performed, the new information is merged into all the information obtained previously. The framework is validated using a laboratory-scale bamboo cantilever beam. The experimental validation showed the potential of the proposed framework for effectively assessing and tracking localized structural conditions by heterogeneous sources of information.

Smart cities employ technology and data to increase efficiencies, economic development, sustainability, and life quality for citizens in urban areas. Inevitably, clean technologies promote smart cities development including for energy, transportation and health. The smart city concept is ambitious and is being refined with standards. Standards are used to help with regulating how smart cities function and contributing to define a smart city. Smart cities must be officially recognized by national and international authorities and organizations in order to promote societal advancement. There are many research and review articles on smart cities. However, technical standards are seldom discussed in the current literature. This review firstly presents the study of smart city definitions and domain. The well-known smart city standards will be presented to better recognize the smart city concept. Well-defined standards allow meaningful comparisons among smart cities implementation. How smart city initiatives make a city smarter and improve the quality of life will be discussed for various countries. This review highlights that technical standards are important for smart cities implementation. This paper serves as a guide to the most recent developments of smart cities standards.

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder, and show a striking male bias in prevalence. Vitamin A (VA) is essential for brain development, and abnormalities in its metabolite retinoic acid are associated with the pathophysiology of ASD. This national multicenter study was conducted to investigate the relationship between serum VA level and core symptoms in ASD children and whether there are still sex differences.MethodA total of 1,300 children with ASD and 1,252 typically-developing (TD) controls aged 2–7 years old from 13 cities in China were enrolled in this study. The symptoms of children with ASD were evaluated by the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS). The neurodevelopmental level of the children was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). The serum level of VA was measured by high-performance liquid chromatography (HPLC).ResultsThe serum VA level in children with ASD was significantly lower than that in TD children, especially in boys with ASD. Furthermore, VA levels in male children with ASD were lower than those in female children with ASD. In addition, we found that serum VA level was negatively correlated the SRS, CARS and communication warming behavior of CBNS-R2016 scores in boys with ASD. In terms of developmental quotients, serum VA level was positively associated with the general quotient, language quotient, gross motor quotient and personal-social quotient of boys with ASD, but no difference was found in girls with ASD.ConclusionsASD children, especially boys, have lower serum VA levels than TD children. Moreover, serum VA status is more commonly associated with clinical symptoms and neurodevelopment in boys with ASD.

IntroductionThis study aimed to investigate the prevalence of developmental regression in children with Autism Spectrum Disorder (ASD) and to explore its relationship with disease severity.MethodsWe finally included 1,027 ASD children aged 2–5 years from 13 cities in China: 138 with regressive ASD and 889 with non-regressive ASD. The Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) were used to evaluate the core symptoms and developmental status of children in the two groups.ResultsAmong the 1,027 ASD children eventually included, 138 (13.44%) cases showed regressive behavior and the average regression occurring age was 24.00 (18.00–27.00) months. Among the regressive children, 105 cases (76.09%) had language regression, 79 cases (57.25%) had social regression, and 4 cases (2.90%) had motor regression. The total scores of ABC and the sub-score of sensory and stereotypic behavior (β = 5.122, 95% CI: 0.818, 9.426, P < 0.05; β = 1.104, 95% CI: 0.120, 2.089, P < 0.05; β = 1.388, 95% CI: 0.038, 2.737, P < 0.05), the SRS total scores and the sub-score of autistic mannerisms (β = 4.991, 95% CI: 0.494, 9.487, P < 0.05; β = 1.297, 95% CI: 0.140, 2.453, P < 0.05) of children in the regressive group were all higher than the non-regressive group. The total developmental quotient (DQ) of CNBS-R2016 and the DQ of gross motor, fine motor, adaptive behavior, language (β = −5.827, 95% CI: −11.529, −0.125, P < 0.05) and personal society in the regressive group were lower than the non-regressive group and the proportion of children with intelligent developmental impairment was higher the non-regressive group.ConclusionRegressive autism is mainly manifested as language and social regression. Children with regressive ASD have more severe core symptoms, lower neurodevelopmental level DQ, and more serious disease degree than children with non-regressive ASD, which requires further etiological examinations and more clinical attention.

Parvovirus B19 (B19V) is pathogenic to humans and causes various human diseases. However, no antiviral agents or vaccines currently exist for the treatment or prevention of B19V infection. Therefore, developing sensitive and specific methods for B19V infection diagnosis is essential for accurate diagnoses. Previously, a Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas12a (cpf1)-based electrochemical biosensor (E-CRISPR) with a picomole sensitivity for B19V detection was established. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the nonstructural protein 1 (NS1) region of the B19V viral genome (abbreviated B19-NS1 PAND). Benefiting from independent protospacer adjacent motif (PAM) sequences, PfAgo can recognize their target with guide DNA (gDNA) that is easy to design and synthesize at a low cost. In contrast to E-CRISPR, without preamplification with Polymerase Chain Reaction (PCR), the Minimum Detectable Concentration (MDC) of three guide- or single guide-mediated B19-NS1 PAND was about 4 nM, approximately 6-fold more than E-CRISPR. However, when introducing an amplification step, the MDC can be dramatically decreased to the aM level (54 aM). In addition, the diagnostic results from clinical samples with B19-NS1 PAND revealed 100% consistency with PCR assays and subsequent Sanger sequencing tests, which may assist in molecular testing for clinical diagnosis and epidemiological investigations of B19V.

Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

Tension is a key processing parameter in the process of composite fiber tape winding. The fluctuation of tension will affect the accuracy of winding and the performance of winding products, such as stress uniformity, fatigue resistance, strength, compactness and resin content. In view of the winding tension is time-varying and the application of tension needs to be more accurate, a tension calculation model is established. Due to the influence of dynamic performance of tension control system by cogging torque, inverter dead zone, ring gear clearance, friction torque, parameter drift, and measurement noise, an adaptive sliding mode control (ASMC) based on extended state observer (ESO) is proposed. The stability of the closed-loop system is proven by Lyapunov theory, the system state variables is estimated by ESO, and the input dead-zone is compensated by the designed adaptive law. Simulation and experimental results show that ESO-based ASMC improves the robustness and dynamic response performance of the tension control system, and can effectively suppress the chattering of the sliding mode control system. The void content and residual stress of composite products have been improved obviously.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective.Methods: We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups.Results: The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients.Conclusion: We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.

Abstract Background The decreasing suicide rate in China has been regarded as a major contributor to the decline of global suicide rate in the past decade. However, previous estimations on China’s suicide rates might not be accurate, since often they were based on the data from the Ministry of Health’s Vital Registration (“MOH-VR”) System, which is biased towards the better-off population. This study aims to compare suicide data extracted from the MOH-VR System with a more representative mortality surveillance system, namely the Center for Disease Control and Prevention’s Disease Surveillance Points (“CDC-DSP”) System, and update China’s national and subnational suicide rates in the period of 2004–2014. Methods The CDC-DSP data are obtained from the National Cause-of-Death Surveillance Dataset (2004–2014) and the MOH-VR data are from the Chinese Health Statistics Yearbooks (2005–2012) and the China Health and Family Planning Statistics Yearbooks (2013–2015). First, a negative binomial regression model was used to test the associations between the source of data (CDC-DSP/MOH-VR) and suicide rates in 2004–2014. Joinpoint regression analyses and Kitagawa’s decomposition method are then applied to analyze the trends of the crude suicide rates. Results Both systems indicated China’s suicide rates decreased over the study period. However, before the two systems merged in 2013, the CDC-DSP System reported significantly higher national suicide rates (IRR = 1.18, 95% Confidence Interval [CI]: 1.13–1.24) and rural suicide rates (IRR = 1.29, 95% CI: 1.21–1.38) than the MOH-VR System. The CDC-DSP System also showed significant reversing points in 2011 (95% CI: 2006–2012) and 2006 (95% CI: 2006–2008) on the rural and urban suicide trends. Moreover, the suicide rates in the east and central urban regions were reversed in 2011 and 2008. Conclusions The biased MOH-VR System underestimated China’s national and rural suicide rates. Although not widely appreciated in the field of suicide research, the CDC-DSP System provides more accurate estimations on China’s suicide rates and is recommended for future studies to monitor the reversing trends of suicide rates in China’s more developed areas.

Abstract Background Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. Methods Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy. Luciferase assays, cell proliferation assay were performed to identify the targets of miR-200a and the mechanism by which it promotes treatment resistance. Survival analysis was used to evaluate the prognosis value of miR-200a. Results In this study, our results showed ectopic expression of miR-200a promotes chemoresistance in breast cancer cell lines to several chemotherapeutic agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in resistance cancer cells. We found overexpression of miR-200a was closely associated with poor response to preoperative chemotherapy and poor prognosis in breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with miR-200a expression in Breast cancer cell lines. Taken together, these clinical and experimental results demonstrate that miR-200a is a determinant of chemoresistance of breast cancer. Conclusions Upregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.

Toll-like receptor 3 (TLR3) is a receptor recognizing double-stranded RNA (dsRNA) from viruses as well as from lytic mammalian cells. In the present study, we performed a two-stage association study (n = 3,551) and found that the minor alleles of two SNPs (the T-allele of rs5743312 and the T-allele of rs3775296) conferred increased risks of breast cancer incidence. The adjusted odds ratios (ORs) were 2.281 (P = 7.01 × 10−5) and 2.086 (P = 8.69 × 10−5), respectively. Specifically, the susceptibility variants within TLR3 were significantly associated with larger tumor size (adjusted P-values: 0.004 for rs5743312 and 0.004 for rs3775296). Furthermore, we investigated the biological function of the TLR3 protein in breast cancer cell lines. Notably, the stable expression of TLR3 directly inhibited cell proliferation both in vitro and in vivo. We also verified that TLR3 conferred less invasive phenotypes on breast cancer cells by regulating the mRNA expression of a panel of genes. TLR3-mediated inhibition of proliferation was caused by downregulation of the EGFR/PI3K/AKT pathway. In summary, our findings strongly suggest that common genetic changes in the TLR3 gene may influence breast cancer susceptibility and development, and TLR3 plays a negative regulatory role in the initiation and progression of human breast cancer cells, at least in part by downregulating the EGFR/PI3K/AKT pathway.

The design elements considered during the construction of a thermochemical reactor determine its thermal performance. This current study investigated the effect of design elements, such as boundary layer thickness, insulating materials for the outlet tube design and fluid inlet locations of the frustum, on the thermal performance of a proposed syngas production reactor with incident radiation heat transfer through quartz glass. The P1 radiation approximation model and fluid flow in the shallow path were integrated into a proposed radiation model. The result indicated that inlet mass flow rates from 5 × 10−4 to 14 × 10−4 kg/s increased the temperature in the cavity and the outlet. The fluid inlet located at the top of the quartz glass edges was found to have better thermal performance and maximum average outlet temperature. Insulation for fluid inlets tube above the quartz glass edges of the frustum was very important for the prevention of radiation loss through quartz glass and sedimentation of fluid particles around the quartz glass edge, and the facilitation of fast heat transfer towards the internal part of the reactor. The outlet that was a tube designed using an aluminum oxide-type insulator with a 50 mm boundary layer thickness was found to increase the average outlet temperature of the reactor. This study revealed that fluid entry and exit locations on the frustum and proper fluid outlet design were critical for the thermal performance analysis of the solar thermochemical reactor for heat transfer with quartz glass. Findings from this study will be of relevance to chemical and power engineering sectors, as well as academia.

BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

The purpose of this study was to determine the prognostic role of ten eleven translocation (TET) family proteins and DNA glycosylase (TDG) in patients with early breast cancer (EBC).Expression of mRNAs encoding TET1-3 and TDG in 162 breast cancer tissues was quantified using real-time polymerase chain reaction analysis. The general characteristics of patients and clinicopathologic factors were collected. Estimation of patient survival was calculated using the Kaplan-Meier method, and independent prognostic indicators were analyzed using Cox regression analysis.The level of TET1 mRNA was significantly related to overall survival (OS) (P = 0.022). Multivariate analysis shows that the TNM stage was an independent predictor of disease-free survival (DFS) (HR = 1.761, 95% CI: 1.124-2.761, P = 0.014) and OS (HR = 2.135, 95% CI: 1.070-4.263, P = 0.032). Further, in patients with EBC who were treated with anthracyclines, Kaplan-Meier analysis indicates that the levels of TET3 and TDG mRNAs were related to DFS (P = 0.026 and 0.030, respectively), and multivariate analysis reveals that high levels of TET3 (HR = 1.944, 95% CI: 1.029-3.672, P = 0.040) and TDG (HR = 2.178, 95% CI: 1.140-4.163, P = 0.018) mRNAs were independent indicators of favorable DFS.Our study indicates that EBC patients with decreased expression of TET1 mRNA had worse OS and that the levels of TET3 and TDG mRNAs were independent prognostic factors for patients who received anthracycline chemotherapy.