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Objective China's oil and gas exploration is advancing towards the field of shale oil and gas. Overpressure is commonly developed in organic shale, and the lack of prediction methods for shale pore pressure restricts the research on shale oil and gas. Methods This article analyses the physical response characteristics of rock to hydrocarbon generation, pressurization and disequilibrium compaction. Based on density and sound velocity data, the differential responses of hydrocarbon generation pressurization and disequilibrium compaction pressurization were analysed. The hydrocarbon generation pressurization amount is calculated using sound velocity and density, and the disequilibrium compaction is calculated using the density data. Finally, the sound velocity rebound method was established. This article selects the Bodong Depression, which has superior hydrocarbon generation conditions, as a case study. First, comprehensive mudstone compaction curves, loading-unloading curves, and sound velocity-density diagrams are used to comprehensively identify the cause of overpressure. Then, the sound velocity rebound method is used to quantitatively calculate the pressure increase and formation pore pressure of a single well under compaction and hydrocarbon generation, and the results are compared with those of numerical simulations and conventional calculation methods. Results Taking the LD21-A well as an example, shale overpressure is caused by a combination of hydrocarbon generation and disequilibrium compaction. The pressure prediction results show that the overpressure of nonsource rock layers is contributed by the disequilibrium compaction. The overpressure of the source rock formation is contributed by hydrocarbon generation and disequilibrium compaction, with hydrocarbon generation pressurization mainly distributed between 5 MPa and 15 MPa (accounting for approximately 35% to 65%), and the measured pressure point hydrocarbon generation pressurization is 11.09 MPa (accounting for 45%). Conclusion This new method is vital of importance for the research of both shale and conventional oil and gas fields.

Summary: Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298–351 h in cynomolgus monkeys and 55–142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

Abstract DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020. Overall, deleterious germline mutations in DDR genes were detected in 346 patients (80.1%), and in BRCA1/2 were detected in 126 patients (29.2%). The prevalence of deleterious germline mutations in BRCA2 is higher than in other studies (patients are mainly from Eastern China), and so is the mismatch repair genes. We identified three novel BRCA1/2 mutations, two of which probably deleterious (BRCA1 p.K1622* and BRCA2 p.L2987P). Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. In conclusion, our study highlights the necessity of comprehensive germline mutation detection of DNA damage response genes in ovarian cancer patients, which is conducive to patient management and genetic counseling.

The volume of instant delivery has witnessed a significant growth in recent years. Given the involvement of numerous heterogeneous stakeholders, instant delivery operations are inherently characterized by dynamics and uncertainties. This study introduces two order dispatching strategies, namely task buffering and dynamic batching, as potential solutions to address these challenges. The task buffering strategy aims to optimize the assignment timing of orders to couriers, thereby mitigating demand uncertainties. On the other hand, the dynamic batching strategy focuses on alleviating delivery pressure by assigning orders to couriers based on their residual capacity and extra delivery distances. To model the instant delivery problem and evaluate the performances of order dispatching strategies, Adaptive Agent-Based Order Dispatching (ABOD) approach is developed, which combines agent-based modelling, deep reinforcement learning, and the Kuhn-Munkres algorithm. The ABOD effectively captures the system's uncertainties and heterogeneity, facilitating stakeholders learning in novel scenarios and enabling adaptive task buffering and dynamic batching decision-makings. The efficacy of the ABOD approach is verified through both synthetic and real-world case studies. Experimental results demonstrate that implementing the ABOD approach can lead to a significant increase in customer satisfaction, up to 275.42%, while simultaneously reducing the delivery distance by 11.38% compared to baseline policies. Additionally, the ABOD approach exhibits the ability to adaptively adjust buffering times to maintain high levels of customer satisfaction across various demand scenarios. As a result, this approach offers valuable support to logistics providers in making informed decisions regarding order dispatching in instant delivery operations.

Abstract Purpose The most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients. Methods Data from patients with pathologically diagnosed lung cancer at the Zhongshan People’s Hospital Department of Radiotherapy for Thoracic Cancer between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots. Results Age, smoking index, chemotherapy, and whole lung V5/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.89(95% confidence interval 0.83–0.95). The nomogram demonstrated a concordance index of 0.89(95% confidence interval 0.82–0.95) and was well calibrated. Furthermore, the threshold values for high- risk and low- risk were determined to be 154 using the receiver operating curve. Conclusions The developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.

Objectives: Clear aligner therapy (CAT) has been gaining popularity amongst the orthodontic community. No systematic course on CAT has been reported to date. The objectives of this study were to determine practitioners’ knowledge and to offer insights for future tailored courses on CAT. Methods: An online questionnaire was distributed. The questionnaire comprised personal background information, predictability of tooth movement through CAT, and CAT knowledge that practitioners demanded to learn. Four senior expert orthodontists’ answers to the predictability of tooth movement through CAT were averaged to be a standard reference. Descriptive statistics, 1-way analysis of variance (ANOVA), principal component analysis, Student t test, and multivariate logistics regression analysis were performed with significance set at P < .05. Results: In total, 190 practitioners participated in this study. As compared to the standard reference, participants overestimated the predictability of difficult-to-be-achived tooth movements (eg, molar mesialisation; P < .0001). Strategy of managing troubleshooting cases and extraction cases ranked the highest CAT knowledge that participants requested to learn. Practice type, number of completed CAT cases, number of undergoing CAT cases, years of practice, education background, and time of using CAT were the influencing factors of the questions regarding the predictability of tooth movement through CAT and CAT knowledge that were demanded to be learned. Conclusions: The predictability of difficult-to-be-achieved tooth movement through CAT is often overestimated by practitioners with limited clinical experience. Tailored education on CAT, especially managing troubleshooting cases and extraction cases, should be designed for all practitioners.

Clubroot disease, which is caused by the obligate biotrophic protist Plasmodiophora brassicae, leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of infected plants. The identification of crucial regulators of host tumor formation is essential to unravel the mechanisms underlying the proliferation and differentiation of P. brassicae within plant cells. To gain insight into this process, transcriptomic analysis was conducted to identify key genes associated with both primary and secondary infection of P. brassicae in Chinese cabbage. Our results demonstrate that the k-means clustering of subclass 1, which exhibited specific trends, was closely linked to the infection process of P. brassicae. Of the 1610 differentially expressed genes (DEGs) annotated in subclass 1, 782 were identified as transcription factors belonging to 49 transcription factor families, including bHLH, B3, NAC, MYB_related, WRKY, bZIP, C2H2, and ERF. In the primary infection, several genes, including the predicted Brassica rapa probable pectate lyase, RPM1-interacting protein 4-like, L-type lectin-domain-containing receptor kinase, G-type lectin S-receptor-like serine, B. rapa photosystem II 22 kDa protein, and MLP-like protein, showed significant upregulation. In the secondary infection stage, 45 of 50 overlapping DEGs were upregulated. These upregulated DEGs included the predicted B. rapa endoglucanase, long-chain acyl-CoA synthetase, WRKY transcription factor, NAC domain-containing protein, cell division control protein, auxin-induced protein, and protein variation in compound-triggered root growth response-like and xyloglucan glycosyltransferases. In both the primary and secondary infection stages, the DEGs were predicted to be Brassica rapa putative disease resistance proteins, L-type lectin domain-containing receptor kinases, ferredoxin-NADP reductases, 1-aminocyclopropane-1-carboxylate synthases, histone deacetylases, UDP-glycosyltransferases, putative glycerol-3-phosphate transporters, and chlorophyll a-binding proteins, which are closely associated with plant defense responses, biosynthetic processes, carbohydrate transport, and photosynthesis. This study revealed the pivotal role of transcription factors in the initiation of infection and establishment of intracellular parasitic relationships during the primary infection stage, as well as the proliferation and differentiation of the pathogen within the host cell during the secondary infection stage.

Background This work explored the characteristics of the WRKY transcription factor family in Rhododendron henanense subsp. lingbaoense (Rhl) and the expression patterns of these genes under abiotic stress by conducting bioinformatics and expression analyses. Methods RhlWRKY genes were identified from a gene library of Rhl. Various aspects of these genes were analyzed, including genetic structures, conserved sequences, physicochemical properties, cis-acting elements, and chromosomal location. RNA-seq was employed to analyze gene expression in five different tissues of Rhl: roots, stems, leaves, flowers, and hypocotyls. Additionally, qRT-PCR was used to detect changes in the expression of five RhlWRKY genes under abiotic stress. Result A total of 65 RhlWRKY genes were identified and categorized into three subfamilies based on their structural characteristics: Groups I, II, and III. Group II was further divided into five subtribes, with shared similar genetic structures and conserved motifs among members of the same subtribe. The physicochemical properties of these proteins varied, but the proteins are generally predicted to be hydrophilic. Most proteins are predicted to be in the cell nucleus, and distributed across 12 chromosomes. A total of 84 cis-acting elements were discovered, with many related to responses to biotic stress. Among the identified RhlWRKY genes, there were eight tandem duplicates and 97 segmental duplicates. The majority of duplicate gene pairs exhibited Ka/Ks values

Background:Awe promotes altruistic behavior by enhancing the sense of the small self. However, this mediation mechanism has not been consistently replicated, possibly due to variations in the types of awe. No studies have directly examined whether the mediation of the sense of the small self between awe and altruistic behavior holds true in general, or is specific to a certain type of awe induction. Here, we describe an experiment aimed to address this issue.Methods:Two hundred and thirty-five participants were randomly assigned to different emotion groups, including natural awe, social awe, spiritual awe, amusement, and neutrality. After emotional manipulation, the participants were informed of a student’s misfortune and asked to decide how much of their experimental compensation money (RMB 50) they would donate.Results:We observed a promoting effect of awe induction on monetary donation in general, and this effect was similar across the three types of awe. Further mediation analysis indicated that natural awe, uniquely promoted altruistic behavior via the mediation role of the small self.Conclusion:The current study demonstrates the novel insight that, although the different types of awe induction similarly promote altruistic behavior, only natural awe promotes altruistic behavior through increasing sense of the small self.

Abstract Background B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants. Results Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p

Capacitors exhibit exceptional power density, a vast operational temperature range, remarkable reliability, lightweight construction, and high efficiency, making them extensively utilized in the realm of energy storage. There exist two primary categories of energy storage capacitors: dielectric capacitors and supercapacitors. Dielectric capacitors encompass film capacitors, ceramic dielectric capacitors, and electrolytic capacitors, whereas supercapacitors can be further categorized into double-layer capacitors, pseudocapacitors, and hybrid capacitors. These capacitors exhibit diverse operational principles and performance characteristics, subsequently dictating their specific application scenarios. To make informed decisions in selecting capacitors for practical applications, a comprehensive knowledge of their structure and operational principles is imperative. Consequently, this review delved into the structure, working principles, and unique characteristics of the aforementioned capacitors, aiming to clarify the distinctions between dielectric capacitors, supercapacitors, and lithium-ion capacitors.

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the Chinese rose genome and classified into three primary groups and five subgroups based on the structural and phylogenetic characteristics. The analysis of the conserved domains, motifs, and gene structure revealed that the RcWRKY genes within the same group had the same exon–intron organization and composition. Chromosome mapping and gene duplication revealed that the RcWRKY genes were randomly dispersed across seven chromosomes. Fragment duplication and refined selection may have influenced the evolution of the WRKY gene family in Chinese rose. The cis-acting elements in the WRKY promoter region revealed that the RcWRKY genes contained numerous abiotic stress response elements. The results of qRT-PCR revealed that the expression of RcWRKY was tissue-specific, with high expression being observed under drought, heat, and salt stress. Notably, RcWRKY49′s expression increased more than fivefold following salt stress, indicating that it is a crucial gene mediating the salt stress response of Chinese rose. These findings shed light on the regulatory role of RcWRKY in the growth and development of Chinese rose, and they serve as a foundation for future molecular breeding programs and gene discovery.

Abstract Background The predictability of incisor movement achieved by clear aligners among Class II division 2 patients is poorly understood. The aim of this retrospective study was to determine the effectiveness of clear aligners in proclining and intruding upper incisors and its influencing factors. Methods Eligible patients with Class II division 2 malocclusion were included. For clear aligner therapy, three types of incisor movements were designed: proclination, intrusion and labial movement. Pre-treatment and post-treatment dental models were superimposed. The differences between predicted and actual (DPA) tooth movement of incisors were analyzed. Univariate and multivariate linear regression were used to analyze the potential influencing factors. Results A total of 51 patients and their 173 upper incisors were included. Actual incisor proclination and intrusion were less than predicted ones (both P

ObjectivesSocial media use (SMU) increased dramatically during COVID-19 due to policies such as long-term quarantine. Given that SMU has complex effects on individuals’ well-being, this study aimed to explore the relationship between SMU and subjective well-being and the influencing factors in the context of the pandemic in China.MethodsA total of 895 adults (413 males) in different risk areas across China participated in this study. They provided self-reported data on subjective well-being, social media use, adaptive humor, and other demographic variables.ResultsIt revealed that SMU was positively associated with individual well-being, an effect partially mediated by the score of adaptive humor. Furthermore, the effect of SMU on adaptive humor was moderated by trait optimism, with the effect more robust in high (vs. low) optimistic individuals.ConclusionThis study explored the positive effects of SMU on individuals’ well-being, suggesting that individuals may better cope with negative experiences and maintain well-being under quarantine by showing more adaptive humor on social media.

Heat shock proteins (HSPs) play important roles in plant stress resistance, but it is not clear whether small molecular HSPs (sHSPs) are involved in the cold stress resistance of lily flowers. In this study, we cloned LbHSP17.9 and found that its expression was up-regulated under cold stress. When LbHSP17.9 was silenced (TRV2::LbHSP17.9) using virus-induced gene silencing in cut lily flowers, the content of malondialdehyde was increased under 4 °C stress treatment. The catalase (CAT) activity in TRV2::LbHSP17.9 was significantly lower than in TRV2 in the first 7 days, and the peroxidase (POD) activity in TRV2::LbHSP17.9 was significantly lower than in TRV2 after 4 days of 4 °C stress. Further analysis showed that the transcription levels of LbCu/ZnSOD, LbMnSOD and LbCAT in TRV2::LbHSP17.9 were lower than those of TRV2 under 4 °C stress. When LbHSP17.9 was overexpressed in lily petal disks, the OE-LbHSP17.9 disks faded later than the controls at 4 °C and the relative conductivity decreased significantly. Overexpression of LbHSP17.9 in Arabidopsis thaliana resulted in fewer injury symptoms and lower MDA content than wild type under 4 °C stress. Therefore, we speculate that LbHSP17.9 can improve the resistance of lily flowers to cold stress.

Considering the characteristics of abundant source rock formations and heterogeneity in the southwestern part of the Bozhong Sag, Bohai Bay Basin, based on the geochemical and petrographic analysis of source rocks, the methods of ΔlogR series, multiple regression and BP neural network are applied to predict the organic matter abundance under the constraints of sedimentary facies.The BP neural network method is preferably used to predict the total organic carbon content and cracked hydrocarbon content of source rocks in a single well, and then the hydrogen index prediction curve is calculated.Combined with total organic carbon content, the organic phase of each source rock layer is quantitatively described, and the advantages and disadvantages and distribution characteristics of source rocks are analyzed. Results show that the prediction accuracy of BP neural network method is relatively higher. The source rocks in the lower section of the second member of Dongying Formation are featured by kerogen of type Ⅱ2, hydrocarbon index of 125-400 mg/g, TOC content basically less than 3%, and organic facies of BC, C and CD types. The source rocks in the third member of Dongying Formation are featured by kerogen of typesⅡ1 to Ⅱ2. The source rocks in the first, second and third members of Shahejie Formation are featured by kerogen of types Ⅰ to Ⅱ1, TOC content about 3% or higher than 3%, and organic facies of B, BC and C types.The high-quality source rocks of the Shahejie Formation are mainly developed in the central and southern parts of the study area, and are the key areas for further exploration.

Graphene oxide (GO) is widely used in various fields such as improving the performance of cement-based materials and making composite materials due to its large specific surface area and abundant oxygen-containing functional groups. However, it has also caused water pollution. To remove GO in aqueous solution, sepiolite (SEP) was used to adsorb it. The effects of pH, adsorbent quality, GO concentration, temperature and adsorption time on the ability of SEP to adsorb GO were investigated. The materials were characterized by SAP and laser particle size analyzer, and the adsorption performance and mechanism of SEP for GO were further analyzed by XRD, FTIR, SEM, TEM, XPS, AFM, and Zeta potential microscopic tests. The results showed that: 1) Under the conditions of temperature 303 K, pH = 3, adsorbent mass 30 mg, and initial concentration of GO 100 mg/L, the adsorption effect was the best, and the adsorption rate reached 94.8 %. 2) The adsorption reached equilibrium at 2160 min, and the adsorption process was more in line with the pseudo-second-order adsorption kinetic equation, and the adsorption behavior was controlled by chemical effects. 3) The adsorption of SEP to GO is more consistent with the Langmuir and Temkin adsorption isotherm model, and the reaction is a spontaneous, endothermic, and entropy-increasing process. Experiments showed that SEP had a strong adsorption capacity for GO, which provides a reference for the treatment of toxic GO in aqueous solution and the realization of water ecological protection.

Abstract Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors’ depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition.

This article presents the design of a two-dimensional (2D) piston pump flow-distribution port with an overlapped structure that reduces backflow in the pump chamber and pressure ripples at the pump outlet, thus minimizing vibration and noise caused by the high-frequency distribution process of a single two-dimensional (2D) piston pump. We describe the flow distribution structure and operation principle of the 2D pump, create a mathematical model of the pump chamber pressure by using the motion and flow continuity equations of the 2D piston, and use a Matlab program to compile and solve them. The influence of the flow distribution port overlap on the pump chamber pressure and the outlet flow rate was simulated. A prototype was designed and tested on a dynamic performance test bench. Our test bench results show that the flow distribution port overlap can reduce the pressure ripple at the pump outlet, which is consistent with the simulation results.

Downed woody debris (DWD) can alter the chemical and biological properties of forest soils, and this process is affected by the degree of DWD decay. Our aim was to assess the effects of the entire decay process of DWD on the associated soil microbial communities. Here, we examined the differences in soil microbial community size and composition among five decay stages (DC Ⅰ–Ⅴ) of Masson pine (Pinus massoniana Lamb.) at two soil depths in a climate transitional forest and then linked these differences to soil chemical properties. The decay of DWD increased soil total PLFAs, and the complexity of soil microbial networks was highest in stage Ⅱ and then decreased with the decay stage. The relative abundance of fungi increased with the decay stage, while the relative abundance of gram-positive bacteria decreased with the decay stage. The microbial community composition at a soil depth of 0–10 cm was mainly driven by soil pH and organic C (SOC), and at a depth of 10–20 cm, soil pH was the primary determinant of microbial community composition. Our findings suggest that DWD decomposition reduces microbial physiological stress, promotes fungal growth, and stimulates microbial biomass, highlighting the positive impact of DWD on forest soils. Future research is needed to elucidate the universal effects of DWD decomposition on soil properties, especially focusing on the response of soil microbial processes to the decomposition time of DWD.

A circular saw blade is a commonly used tool in wood processing. The transverse vibration of the saw blade plays an important role in processing quality during cutting and affects its service life as well. In the study, the transverse vibration of the circular saw blade was investigated at the constant rotation by the simulation using ANSYS software when changing the cantilever length of the cantilever woodworking CNC circular saw machine. Meanwhile, the transverse vibration of the circular saw blade without and with load was explored by the eddy current sensors for when the detection point was differently away from the center of the circular saw blade. The time domain, probability density distribution, and power spectrum characteristics of the transverse vibration signal were analyzed, and the simulation values were compared with the actual cutting data. The results revealed that under certain conditions, the maximum transverse vibration value of the circular saw blade was the smallest in the simulation, then the middle in no-load, and the largest in actual cutting. The maximum transverse vibration value of the saw blade was increased with the extension of the cantilevered overhang, but gradually and slightly, indicating the transverse vibration was hardly affected by the change in overhang length of less than 300 mm. The finding provides the reference for the structural optimization design of cantilever CNC circular saw machines and the promotion of its application.

Abstract Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague–Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.

Abstract Background Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. Methods Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression. Results Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. Conclusions N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

Drug addiction is a common problem worldwide. Research has shown adverse childhood experiences (ACEs) to be an important factor related to drug addiction. However, there are few studies on how ACEs lead to drug addiction and the role of resilience and depression in this process. Thus, the main purposes of the study were to determine the proportion of those with adverse childhood experiences who take drugs in adulthood and how resilience and depression affect this relationship. The results showed that (1) greater severity of ACEs made individuals more likely to take drugs; (2) ACEs were positively correlated with depression, and resilience was negatively correlated with ACEs and depression; and (3) ACEs not only affected drug addiction through resilience or depression alone but also through the combined action of resilience and depression, indicating that depression led to drug addiction while resilience weakened the effect of ACEs on depression and drug addiction. Furthermore, in the serial mediation model, abuse, neglect, and family dysfunction were significant predictors of drug addiction. Our results are encouraging in that they provide guidance in understanding the complex relationships among ACEs, resilience, depression, and drug addiction.

Background: Lip morphology is essential in diagnosis and treatment of orthodontics and orthognathic surgery to ensure facial aesthetics. Body mass index (BMI) has proved to have influence on facial soft tissue thickness, but its relationship with lip morphology is unclear. This study aimed to evaluate the association between BMI and lip morphology characteristics (LMCs) and thus provide information for personalized treatment. Methods: A cross-sectional study consisted of 1185 patients from 1 January 2010 to 31 December 2020 was conducted. Confounders of demography, dental features, skeletal parameters and LMCs were adjusted by multivariable linear regression to identify the association between BMI and LMCs. Group differences were evaluated with two-samples t-test and one-way ANOVA test. Mediation analysis was used for indirect effects assessment. Results: After adjusting for confounders, BMI is independently associated with upper lip length (0.039, [0.002–0.075]), soft pogonion thickness (0.120, [0.073–0.168]), inferior sulcus depth (0.040, [0.018–0.063]), lower lip length (0.208, [0.139–0.276]), and curve fitting revealed non-linearity to BMI in obese patients. Mediation analysis found BMI was associated with superior sulcus depth and basic upper lip thickness through upper lip length. Conclusions: BMI is positively associated with LMCs, except for nasolabial angle as negatively, while obese patients reverse or weaken these associations.

Bone tissue engineering is a novel and efficient repair method for bone tissue defects, and the key step of the bone tissue engineering repair strategy is to prepare non-toxic, metabolizable, biocompatible, bone-induced tissue engineering scaffolds of suitable mechanical strength. Human acellular amniotic membrane (HAAM) is mainly composed of collagen and mucopolysaccharide; it has a natural three-dimensional structure and no immunogenicity. In this study, a polylactic acid (PLA)/Hydroxyapatite (nHAp)/Human acellular amniotic membrane (HAAM) composite scaffold was prepared and the porosity, water absorption and elastic modulus of the composite scaffold were characterized. After that, the cell–scaffold composite was constructed using newborn Sprague Dawley (SD) rat osteoblasts to characterize the biological properties of the composite. In conclusion, the scaffolds have a composite structure of large and small holes with a large pore diameter of 200 μm and a small pore diameter of 30 μm. After adding HAAM, the contact angle of the composite decreases to 38.7°, and the water absorption reaches 249.7%. The addition of nHAp can improve the scaffold’s mechanical strength. The degradation rate of the PLA+nHAp+HAAM group was the highest, reaching 39.48% after 12 weeks. Fluorescence staining showed that the cells were evenly distributed and had good activity on the composite scaffold; the PLA+nHAp+HAAM scaffold has the highest cell viability. The adhesion rate to HAAM was the highest, and the addition of nHAp and HAAM could promote the rapid adhesion of cells to scaffolds. The addition of HAAM and nHAp can significantly promote the secretion of ALP. Therefore, the PLA/nHAp/HAAM composite scaffold can support the adhesion, proliferation and differentiation of osteoblasts in vitro which provide sufficient space for cell proliferation, and is suitable for the formation and development of solid bone tissue.

Abstract Background Immunity reaction plays an essential role in periodontitis progress and we aim to investigate the underlying regulatory network of immune reactions in periodontitis. Methods CIBERSORT was used to estimate immunocyte fractions in different clinical statuses. Logistic regression was used to assess the immunocyte weight in periodontitis. Immune-related periodontitis subtypes were identified by the Nonnegative Matrix Factorization algorithm. Gene-set enrichment analysis and Gene-set variation analysis were conducted to analyze pathway activities. Immunocytes related gene modules were identified by Weighted gene co-expression network analysis. Results Altered immunocytes in healthy versus periodontitis, aggressive versus chronic, male versus female and age were identified. Immunocytes enriched in periodontitis were calculated, and their correlation was also explored. Two distinct immune-related periodontitis subtypes were identified and one is characterized by B cell reactions and the other is IL-6 cytokine reactions. 463 statistically significant correlations between 22 immunocytes and pathways were revealed. Immunocytes and clinical phenotypes matched their gene modules, and their functions were annotated. Last, an easy-to-use and user-friendly interactive web-tool were developed for periodontitis related immune analysis and visualization ( https://118.24.100.193:3838/tool-PIA/ ). Conclusions This study systematically investigated periodontitis immune atlas and caught a glimpse of the underlying mechanism of periodontitis from gene-pathway-immunocyte networks, which can not only inspire researchers but also help them in periodontitis related immune researches.

Abstract Background Recent years have witnessed a remarkable evolution of clear aligner technology and clear aligners are becoming more and more versatile in treating orthodontic patients. The aim of this study was to develop an objective evaluation system for assessing clear aligner treatment difficulty. Methods A total of 120 eligible patients (100 patients for developing and testing the evaluation system and 20 patients for validating this system) were recruited in this retrospective cross-sectional study. Based on clinical data (dental models, radiographs and photographs), complexity levels of cases were evaluated by two experts and regarded as the gold standard. Difficulty scores were determined through an evaluation system encompassing three domains (dental model analysis, radiographic examinations and clinical examinations). The reliability of the evaluation system was examined through analyzing the agreement between complexity levels and difficulty scores. Moreover, multivariable linear regression test was used to examine the independent association of each variable (e.g. overbite and crowding) with the complexity level. Results The results revealed that the assessment of treatment difficulty by this objective evaluation system substantially matched the gold standard (R2 = 0.80). The multivariable regression test revealed that complexity level was significantly associated with difficulty score (p

The sandstone reservoirs in the Upper Paleozoic He 8 Member in the northern Tianhuan depression of the Ordos Basin are vastly different and feature particularly complex gas–water distributions. Scanning electron microscopy, fluorescence, Raman spectroscopy inclusions, relative permeability analysis, and nuclear magnetic resonance were utilized in this study based on core data, identification statistics, and various thin-section microscope measurements. Samples from the Upper Paleozoic He 8 Member in the northern Tianhuan depression were collected to study the characteristics of reservoir heterogeneity and gas–water distribution, which were controlled by differential diagenesis. The results indicate that compaction and dissolution are the two most important factors controlling reservoir heterogeneity. Large differences in diagenesis–accumulation sequences and pore structure characteristics affect reservoir wettability, irreducible water saturation, and gas displacement efficiency, thereby controlling the gas–water distribution. The He 8 Member is a gas reservoir that is densified because of accumulation. Reservoirs can be divided into three types based on the relationship between diagenetic facies and gas–water distribution. Type I is characterized by weak compaction, precipitate or altered kaolinite cementation, strong dissolution of diagenetic facies, and high porosity and permeability. This type is dominated by grain-mold pores and intergranular dissolution pores and produces gas reservoirs with high gas yield. Type II is characterized by medium-strength compaction, altered kaolinite or chlorite cementation, weak dissolution of diagenetic facies, and medium porosity and permeability. This type is dominated by residual intergranular pores, a few residual intergranular pores, and dispersed dissolution pores, producing gas reservoirs with low gas yield. Type III is characterized by medium-strength compaction, altered kaolinite cementation, and medium-strength dissolution of diagenetic facies. This type is dominated by kaolinite intercrystal pores and dispersed dissolution pores, producing gas reservoirs with high water yield.

BackgroundHodgkin lymphoma survivors are at risk for second malignant neoplasm (SMN). How race/ethnicity affects the risk remains unclear.MethodsThis retrospective cohort study included 22,415 patients diagnosed with primary Hodgkin lymphoma from January 1992 to December 2015 in 13 Surveillance, Epidemiology, and End Results-based registries and divided patients into four groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, and Asian/others. Taking non-Hispanic whites as a reference, both the proportional subdistribution hazard (PSH) and the cause-specific hazard (CSH) methods were used to calculate the SMN hazard ratio for other racial/ethnic groups with and without considering the competing mortality risk.Results1,778 patients developed SMN with a median follow-up of 11.63 years. In the adjusted PSH model, Hispanic, Asian/others, and non-Hispanic black patients had 26% (PSH, 0.74; 95% CI, 0.63–0.87), 20% (PSH, 0.80; 95% CI, 0.64–1.01), and 12% (PSH, 0.88; 95% CI, 0.75–1.03) decreased overall SMN hazard, respectively. Moreover, the PSH method revealed the racial/ethnic difference in the SMN risk in the skin, the respiratory system, and the endocrine system. These hazards were slightly higher and different with the use of the CSH approach. In addition to the aforementioned overall SMN and subtypes, adjusted CSH analysis also revealed the racial/ethnic disparities in the risk of subsequent female breast cancer, digestive cancer, and non-Hodgkin lymphoma.ConclusionsThe subtype and SMN risk among Hodgkin lymphoma survivors varied by race/ethnicity. The use of CSH and PSH provides a dynamic view of racial/ethnic effects on SMN risk in Hodgkin lymphoma survivors.

Abstract Background Allergic rhinitis (AR) is a common allergic disease. It affects people worldwide and traditional Chinese medicine is becoming popular among AR patients because it has a definite clinical effect and there are few adverse reactions. Lung qi deficiency and cold syndrome (LQDCS) is a frequent type of AR, and the Chinese herbal medicine bimin decoction (BMD) is prescribed for it. This study compared the clinical efficacy of BMD for AR patients with LQDCS to the conventional medicine loratadine and fluticasone nasal spray. Methods The study was an open-label non-inferiority randomized controlled trial. A total of 108 AR patients with LQDCS aged 19 to 60 were randomly allocated in a 1:1 ratio to the BMD group or the control group by the central computer system in Beijing Hospital of Traditional Chinese Medicine from January 2017 to April 2018. In total, 98 participants completed the study (BMD group n = 51 and control group n = 47). Patients in the BMD group received BMD while those in the control group received fluticasone nasal spray and loratadine tablets for 4 weeks. The primary outcome was the change in the Total Nasal Symptom Score (TNSS) between the baseline and the end of treatment. Changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal resistance, and acoustic rhinometry parameters were secondary outcomes. All side effects due to the treatments were recorded. Results After the 4-week treatment, the total TNSS was significantly reduced in both groups compared to the baseline (P 0.05). Conclusions These findings indicate that BMD helps relieve the symptoms of perennial AR and improves rhinitis-related quality of life. Our study indicates that BMD is non-inferior to loratadine tablets and fluticasone nasal spray for AR patients with LQDCS. Trial registration Chinese Clinical Trial Registry, ChiCTR-INR-16010063. Registered on 2 December 2016.

Road extraction from high-resolution remote sensing images (HRSIs) is essential for applications in various areas. Although deep convolutional neural networks (DCNNs) have exhibited remarkable success in road extraction, the performance relies on a large amount of training samples which are hard to obtain. To address this issue, multiple crowdsourced data are used in this study, including OpenStreetMap (OSM), Zmap and GPS. And a multi-map integration model (MMIM) is developed to improve the noise robustness of DCNNs for road extraction tasks. Specifically, rich geographical road information are obtained from multiple crowdsourced data, including main roads, new construction roads, midsize and small roads, which can generate complete road training samples and reduce the label noise. Meanwhile, by exploring the true road label information hidden in different crowdsourced data, the MMIM is used to generate high-quality refined labels for learning DCNNs. In this case, the DCNN-based road extraction methods have more opportunities to learn true road distribution and avoid the overfitting problems of label noise. Experiments based on real road extraction dataset indicate that the proposed method shows great performance, and road extraction results are smoother and more complete.

In the process of orthodontic treatment, root parallelism is related to the relapse of extraction spaces, black triangles, and periodontal health. However, there are few studies on root parallelism in extraction cases with different types of appliances. The objective was to compare the root parallelism in extraction cases treated with clear aligners vs. those treated with fixed appliances by measuring the differences per extraction site and to access the root-movement control capacity of both orthodontic appliances. A retrospective study was conducted on cases in which the first premolars were extracted, treated by clear aligner appliance (“Invisalign” system, 28 patients) or fixed appliance (30 patients). The angulations of the tooth axis (canines, the second premolars, the first molars, and the second molars) were measured to analyze and compare the difference in root parallelism between the two orthodontic appliances. The percentage of root parallelism between the canine and second premolar in both groups had no significant difference. However, judging from the average angle difference value, the fixed appliance might have a greater range in root angulation adjustment than the aligner. In the angulation categories, the aligner mainly showed root apical divergence, while the fixed appliance mainly showed root apical convergence. The dental crown of the molars was mainly non-tipping in both groups, but it could be observed that the dental crown of the maxillary molars had a tendency toward mesial inclination. In conclusion, the same root parallelism and root inclination were obtained in tooth extraction cases whether treated by clear aligners or fixed appliances. This study provides clinicians with more information on the performance of clear aligners and fixed appliances.

The apextrin C-terminal (ApeC) domain is a class of newly discovered protein domains with an origin dating back to prokaryotes. ApeC-containing proteins (ACPs) have been found in various marine and aquatic invertebrates, but their functions and the underlying mechanisms are largely unknown. Early studies suggested that amphioxus ACP1 and ACP2 bind to bacterial cell walls and have a role in immunity. Here we identified another two amphioxus ACPs (ACP3 and ACP5), which belong to the same phylogenetic clade with ACP1/2, but show distinct expression patterns and sequence divergence (40-50% sequence identities). Both ACP3 and ACP5 were mainly expressed in the intestine and hepatic cecum, and could be up-regulated after bacterial challenge. Both prokaryotic-expressed recombinant ACP3 and ACP5 could bind with several species of bacteria and yeasts, showing agglutinating activity but no microbicidal activity. ELISA assays suggested that their ApeC domains could interact with peptidoglycan (PGN), but not with lipoteichoic acid (LTA), lipopolysaccharides (LPS) and zymosan A. Furthermore, they can only bind to Lys-type PGN from Staphylococcus aureus, but not to DAP-type PGN from Bacillus subtilis and not to moieties of PGN such as MDPs, NAMs and NAGs. This recognition spectrum is different from that of ACP1/2. We also found that when expressed in mammalian cells, ACP3 could interact with TRAF6 via a conserved non-ApeC region, which inhibited the ubiquitination of TRAF6 and hence suppressed downstream NF-κB activation. This work helped define a novel subfamily of ACPs, which have conserved structures, and have related yet diversified molecular functions. Its members have dual roles, with ApeC as a lectin and a conserved unknown region as a signal transduction regulator. These findings expand our understanding of the ACP functions and may guide future research on the role of ACPs in different animal clades.

Abstract Background Normal distribution of body fluid is important for maintaining health through the balance of water metabolism. Studies have shown that disease states and diuretics perturb the balance and then induce abnormal intracellular/extracellular fluid ratio. However, there are relatively few researches on the associations between water intakes and body fluid. The objective of this study was to explore the association between body fluid and water intake. Methods A total of 159 young adults in Baoding, China were recruited in this cross-sectional survey and completeness of follow-up was 98.1%. A 7-day fluid specific diary was used to record total fluid intake (TFI). Water intake from foods (FWI) for 3 days was measured using the methods of weighting, duplicate portion method and laboratory analysis by researchers. Body fluid was measured using bioelectrical impedance analysis. Results Total body water (TBW), intracellular fluid (ICF) and extracellular fluid (ECF) of participants were 32.8[28.0,39.2], 20.5[17.3,24.5] and 12.4[10.7,14.7], (kg). This represented 55.2 ± 6.2, 34.4 ± 4.0 and 20.8 ± 2.3 (%) of body weight (BW), respectively. ICF, ECF and TBW among male participants who drank more than or equal to adequate TFI was higher than those who drank less (Z = -1.985, p = 0.047; Z = -2.134, p = 0.033; Z = -2.053, p = 0.040). Among both males and females, the values of TBW/BW in participants whose TWI met or exceeded the AI were higher than those with TWI less than AI (t = − 2.011, p = 0.046; t = − 2.716, p = 0.008). Among all participants, there was moderate correlation between water intakes (TFI/BW, FWI/BW and TWI/BW) and body fluid (ICF/BW,ECF/BW and TBW/BW) (p

Abstract Background Visceral adiposity has been reported to play a key role in hypertension compared with other measurements of regional or general obesity. The aim of current study was to evaluate the relationship between visceral fat reduction and changes in blood pressure in a group of overweight or obese Chinese individuals. Methods An observational study was conducted with 168 participants (ChiCTR-OOC-17012000). Body composition, blood parameters and blood pressure were assessed at the beginning and end of the intervention. Males and females were categorized separately into quartiles according to changes in visceral fat during the intervention. Multiple linear regression models were used to assess the associations of changes in systolic and diastolic blood pressure with changes of visceral fat area, adjusted for potential confounders. Results Changes in visceral fat was significantly associated with systolic and diastolic blood pressure in men for systolic (β = 0.234, 95% CI: 0.103, 0.365; p = 0.001) and diastolic blood pressure (β = 0.237; 95% CI: 0.127, 0.346; p

Abstract Background The direct and indirect bonding techniques are commonly used in orthodontic treatment. The differences of the two techniques deserve evidence-based study. Materials and methods Randomized controlled trials (RCTs), wherein direct and indirect bonding techniques were used in orthodontic patients were considered. The MEDLINE, EMBASE, CENTRAL and Web of Science databases were searched to identify relevant articles published up to December 2018. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using the data collection form. The included trials were assessed using the Cochrane risk of bias assessment tool. Results Of the 1557 studies screened, 42 full articles were scrutinized and assessed for eligibility. Eight RCTs (247 participants) were finally included for the analyses. The qualitative synthesis showed that no significant difference existed in the accuracy of bracket placement and oral hygiene status between the two bonding techniques. The indirect bonding was found to involve less chairside time but more total working time compared with the direct bonding. The meta-analysis on bond failure rate demonstrated no significant difference between the direct and indirect bonding (RR = 1.13, 95% CI = 0.78–1.64, I2 = 22%, P = 0.50). Consistent results were obtained in the subgroup analyses and sensitivity analyses. Conclusion Weak evidence suggested that the direct and indirect bonding techniques had no significant difference in bracket placement accuracy, oral hygiene status and bond failure rate, for bonding orthodontic brackets. The indirect bonding might require less chairside time but more total working time in comparison with the direct bonding technique. High-quality well-designed randomized controlled trials are needed before a conclusive recommendation could be made.

Abstract High electrochemical performance of asymmetric supercapacitor (ASC) depends on exquisite nanostructure design and synthesis of electrodes, including structural controllable design and synthesis of high theoretical performance materials and nanocomposite materials. Herein, a template-free hierarchical core-shell nanostructure of CoNiO2@NiAl-layered double hydroxide (NiAl-LDH) and α-Fe2O3 with a hollow spherical structure composed of nanoparticles are successfully prepared. The CoNiO2@NiAl-LDH as the cathode electrode and the hollow spherical α-Fe2O3 as the anode electrode of the ASC devices exhibit superior electrochemical performance. The gel of polyvinyl alcohol (PVA) and KOH acts as the solid electrolyte and the separator to assemble into the all-solid-state flexible ASC devices. Two of the CoNiO2@NiAl-LDH//α-Fe2O3 ASC devices in series are fabricated to meet the voltage requirement of mobile energy equipment, which exhibit a maximum energy density of 65.68 Wh kg−1 at the power density of 369.45 W kg−1. Interestingly, in addition to many advantages that the solid electrolyte in ASC devices already have, we find that it can be an alternative way of solving the problem of iron oxide cycling performance, and of course it can also be used as a reference for other materials with poor cycling performance.

Drought has been approved to affect the process of terrestrial ecosystems from different organizational levels, including individual, community, and ecosystem levels; however, which traits play the dominant role in the resistance of plant to drought is still unclear. The experiment was conducted in semi-arid temperate grassland and included six paired control and drought experimental plots. The drought treatment was completely removed from precipitation treatments from 20 June to 30 August 2013. At the end of the growing season in 2013, we removed the rain cover for ecosystem recovery in 2014. The results demonstrated that drought treatment increased the coverage of and abundance Heteropappus altaicus, Potentilla bifurca, and Artemisia scoparia by 126.2–170.0% and 63.4–98.9%, but decreased that of Artemisia frigida, Dontostemon dentatus, and Melissilus ruthenicu by 46.2–60.2% and 49.6–60.1%. No differences in coverage and abundance of Agropyron cristatum, Stipa kiylovii, and Cleistogenes squarrosa were found between control and drought treatment. The coverage and abundance of Stipa kiylovii have exceeded the original level before the drought stress, but Heteropappus altaicus still had not recovered in the first year after the disturbance. Our findings indicate that plant functional traits are important for the understanding of the resistance and resilience of plants to drought stress, which can provide data support for grassland management.

Objective: The purpose of this study is to evaluate whether the impulse inhibition ability with methamphetamine dependents would vary at different abstinence stages.Methods: Sixty-three methamphetamine dependents, including 31 short-term (< 10 months) and 32 long-term (≥ 10 months) abstinence participants, were recruited for this study. In addition, 33 men were recruited as the healthy control (HC) group. All participants performed a two-choice oddball task, which is well-established to assess impulse inhibition. Accuracy for deviant trials and deviant–standard reaction time (RT) delay were computed as indexes of impulse inhibition.Results: The accuracy for deviant trials was significantly decreased in short-term abstinence subjects (90.61%) compared to HC subjects (95.42%, p < 0.01), which was coupled with a shorter RT delay reflecting greater impulsivity in the short-term group vs. the HC group (47 vs. 73 ms, p < 0.01). However, impulse inhibition was improved in the long-term group, shown by the increased accuracy for deviant trials in the long-term group compared to the short-term group (94.28 vs. 90.61%, p < 0.05) and the similar accuracy for the long-term and HC groups (p > 0.05). Further regression analyses confirmed that the abstinence duration positively predicted impulse inhibition of methamphetamine dependents, both in accuracy and RT for deviant stimulus (β = 0.294, p = 0.019; β = 0.337, p = 0.007).Conclusion: These results suggest that long-term abstinence is more effective in improving impulse inhibition with methamphetamine dependents.

This study aims to evaluate the overall bone thickness (OBT) and cortical bone thickness (CBT) of mandibular symphysis and to determine the optimal sites for the insertion of orthodontic mini implants. Cone-beam computed tomography (CBCT) images of 32 patients were included in this study. The sample was further categorized into three facial types: low-, average-, and high-angle. OBT and CBT were measured at the mandibular symphysis region. All measurements were performed at six different heights from the cementoenamel junction [CEJ] and at seven different angles to the occlusal plane. Analysis of variance (ANOVA) was used for statistical comparison and a p value less than 0.05 was considered statistically significant. Our results revealed that neither OBT nor CBT was influenced by age or sex, except for the observation that CBT was significantly greater in adults than in adolescents. OBT and CBT were significantly greater in low-angle cases than in average- and high-angle cases. Both OBT and CBT were significantly influenced by insertion locations, heights and angles, and their interactions. CBT and OBT were greatest at the location between two lower central incisors, and became greater with increases in insertion height and angle. Both recommended and optimal insertion sites were mapped. The mandibular symphysis region was suitable for the placement of orthodontic mini implants. The optimal insertion site was 6–10 mm apical to the CEJ between two lower central incisors, with an insertion angle being 0–60 degrees to the occlusal plane.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children with distinct characteristics among different subtypes. Although the etiology of ALL has not been fully unveiled, initiation of ALL has been demonstrated to partly depend on genetic factors. As indicated by several genome wide association studies (GWASs) and candidate gene analyses, ARID5B, a member of AT-rich interactive domain (ARID) protein family, is associated with the occurrence and prognosis of ALL. However, the mechanisms by which ARID5B genotype impact on the susceptibility and treatment outcome remain vague. In this review, we outline developments in the understanding of ARID5B in the susceptibility of ALL and its therapeutic perspectives, and summarize the underlying mechanisms based on the limited functional studies, hoping to illustrate the possible mechanisms of ARID5B impact and highlight the potential treatment regimens.

Background: Upper lip morphology is essential in diagnosis and treatment of orthodontics and orthognathic surgery. This study is aimed to evaluate the association between upper lip characteristics (ULCs) and skeletal patterns (SPs). Methods: 2079 patients were involved and grouped by sagittal and vertical. Class I, II, and III were identified by ANB angle, while normodivergent, hyperdivergent, and hypodivergent were identified by Facial Height Index and Sum of Angles. ULCs were evaluated by superior sulcus depth, nasolabial angle, upper lip length, basic upper lip thickness, and upper lip thickness. Confounders including demography, malocclusion, upper incisors, and upper lips were adjusted by multivariate linear regression to identify the association between ULCs and SPs. Group differences were evaluated with analysis of variance and Chi-square test. Results: The mean value of ULCs and prevalence of SPs were explored in the Western China population. ULCs were significantly different in various sagittal, vertical, and combined SPs. Superior sulcus depth was negatively related to Class II, and positively related to Class III and the hypodivergent pattern after adjusted by confounders. Conclusions: ULCs significantly varied among different SPs, while only superior sulcus depth was independently associated with SPs, indicating superior sulcus depth is the only ULC that might be significantly corrected by intervention of skeletal growth.

Pomegranate (Punica granatum L.) is one of the most important fruit trees in semi-arid land. Previous studies were primarily focused on soil microbial community composition under different pomegranate plantation managements. However, soil microbial community composition under long-term pomegranate plantation has rarely been studied. We investigated pomegranate plantation along with an age sequence (i.e., 1, 3, 5, and 10 years after pomegranate plantation; abbreviated by P1, P3, P5, P10, respectively) in the Middle Yellow River floodplain. Our objectives were to address (1) variations of soil physicochemical properties and (2) changes in soil microbial community composition and the influential factors. The results demonstrated that the soil water content of pomegranate plantation decreased with the increase of pomegranate plantation stand age. Specifically, dissolved organic carbon, ammonium, and available phosphorus increased significantly with stand age both at 0–10- and 10–20-cm soil depths. The P10 had the highest microbial phospholipid fatty acid (PLFA) profiles, including fungi, bacteria, Gram-positive bacteria, Gram-negative bacteria, and arbuscular mycorrhizal fungi. The ratio of fungal PLFAs to bacterial PLFAs increased and the ratio of Gram-positive to Gram-negative bacterial PLFAs decreased along the pomegranate plantation stand age. Dissolved organic carbon was the most important influential factor among the studied variables, which explained 42.2% variation of soil microbial community. In summary, the long-term plantation of pomegranate elevated soil microbial biomass and altered microbial community composition.

Germline variants of PIP4K2A impact susceptibility of acute lymphoblastic leukemia (ALL) through inducing its overexpression. Although limited reports suggested the oncogenic role of PIP4K2A in cancers, regulatory network and prognostic effect of this gene remains poorly understood in tumorigenesis and leukemogenesis. In this study, we conducted genome-wide gene expression association analyses in pediatric B-ALL cohorts to discover expression associated genes and pathways, which is followed by the bioinformatics analyses to investigate the prognostic role of PIP4K2A and its related genes in multiple cancer types. 214 candidates were identified to be significantly associated with PIP4K2A expression in ALL patients, with known cancer-related genes rankings the top (e.g., RAC2, RBL2, and TFDP1). These candidates do not only tend to be clustered in the same types of leukemia, but can also separate the patients into novel molecular subtypes. PIP4K2A is noticed to be frequently overexpressed in multiple other types of leukemia and solid cancers from cancer cohorts including TCGA, and associated with its candidates in subtype-specific and cancer-specific manners. Interestingly, the association status varied in tumors compared to their matched normal tissues. Moreover, PIP4K2A and its related candidates exhibit stage-independent prognostic effects in multiple cancers, mostly with its lower expression significantly associated with longer overall survival (p < 0.05). Our findings reveal the transcriptional regulatory network of PIP4K2A in leukemia, and suggest its potentially important role on molecular subtypes of multiple cancers and subsequent treatment outcomes.

Checkpoint inhibitor (CPI) based immunotherapy (i.e., anit-CTLA-4/PD-1/PD-L1 antibodies) can effectively prolong overall survival of patients across several cancer types at the advanced stage. However, only part of patients experience objective responses from such treatments, illustrating large individual differences in terms of both efficacy and adverse drug reactions. Through the observation on a series of CPI based clinical trials in independent patient cohorts, associations of multiple clinical and molecular characteristics with CPI response rate have been determined, including microenvironment, genomic alterations of the cancer cells, and even gut microbiota. A broad interest has been drawn to the question whether and how these prognostic factors can be used as biomarkers for optimal usage of CPIs in precision immunotherapy. Therefore, we reviewed the candidate prognostic factors identified by multiple trials and the experimental investigations, especially those reported in the recent 2 years, and described the possibilities and problems of them in routine clinical usage of cancer treatment as biomarkers.

Meal replacement plans are effective tools for weight loss and improvement of various clinical characteristics but not sustainable due to the severe energy restriction. The aim of the study was to evaluate the impact of meal replacement, specifically 388 kcal in total energy, on body composition and metabolic parameters in individuals with overweight and obesity from a Chinese population. A parallel, randomized controlled trial was performed with 174 participants (ChiCTR-OOC-17012000). The intervention group (N=86) was provided with a dinner meal replacement, and the control group (N=88) continued their routine diet as before. Body composition and blood parameters were assessed at 0, 4, 8, and 12 weeks. A post hoc analysis (least significant difference (LSD) test), repeated measurements, and paired T-test were used to compare each variable within and between groups. Significant (p

Movie highlights are composed of video segments that induce a steady increase of the audience’s excitement. Automatic movie highlights’ extraction plays an important role in content analysis, ranking, indexing, and trailer production. To address this challenging problem, previous work suggested a direct mapping from low-level features to high-level perceptual categories. However, they only considered the highlight as intense scenes, like fighting, shooting, and explosions. Many hidden highlights are ignored because their low-level features’ values are too low. Driven by cognitive psychology analysis, combined top-down and bottom-up processing is utilized to derive the proposed two-way excitement model. Under the criteria of global sensitivity and local abnormality, middle-level features are extracted in excitement modeling to bridge the gap between the feature space and the high-level perceptual space. To validate the proposed approach, a group of well-known movies covering several typical types is employed. Quantitative assessment using the determined excitement levels has indicated that the proposed method produces promising results in movie highlights’ extraction, even if the response in the low-level audio-visual feature space is low.