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Abstract Objective This study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy. Methods A total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications. Results The use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p

Abstract Companion planting of white clover (Trifolium repens L.) with orchard grass (Dactylis glomerata L.), a famous hay grass, improves the forage quality of orchard grass. Microbiome profiling techniques can reveal the specific role of white clover companion planting with orchard grass. This study aimed to explore the microbiome distribution and gene functions of rhizosphere and non-rhizosphere soil via companion planting systems of white clover and orchard grass. From metagenomics sequencing analysis, we confirmed the significant role of white clover on soil environment modeling during companion planting with orchard grass. Twenty-eight biomarkers of rhizosphere soil organisms were identified during companion planting, including Proteobacteria, Betaproteobacteria, Flavobacteriia, and Caulobacterales. The number of gene functions of nitrogen and carbon fixation in companion planting was higher than that in single plants, indicating new functional flora for companion planting. We characterized specific rhizosphere effects, typical biomarker flora, and potential regulatory mechanisms for white clover-related companion planting by metagenomics analyses.

When employing penetration ammunition to strike multi-story buildings, the detection methods using acceleration sensors suffer from signal aliasing, while magnetic detection methods are susceptible to interference from ferromagnetic materials, thereby posing challenges in accurately determining the number of layers. To address this issue, this research proposes a layer counting method for penetration fuze that incorporates multi-source information fusion, utilizing both the temporal convolutional network (TCN) and the long short-term memory (LSTM) recurrent network. By leveraging the strengths of these two network structures, the method extracts temporal and high-dimensional features from the multi-source physical field during the penetration process, establishing a relationship between the multi-source physical field and the distance between the fuze and the target plate. A simulation model is developed to simulate the overload and magnetic field of a projectile penetrating multiple layers of target plates, capturing the multi-source physical field signals and their patterns during the penetration process. The analysis reveals that the proposed multi-source fusion layer counting method reduces errors by 60% and 50% compared to single overload layer counting and single magnetic anomaly signal layer counting, respectively. The model's predictive performance is evaluated under various operating conditions, including different ratios of added noise to random sample positions, penetration speeds, and spacing between target plates. The maximum errors in fuze penetration time predicted by the three modes are 0.08 ms, 0.12 ms, and 0.16 ms, respectively, confirming the robustness of the proposed model. Moreover, the model's predictions indicate that the fitting degree for large interlayer spacings is superior to that for small interlayer spacings due to the influence of stress waves.

BackgroundExtranodal Non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to explore the clinical features and prognostic factors of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL), in order to provide new references for basic research and clinical diagnosis and treatment of the rare extranodal malignant lymphoma.MethodsThe clinical data of 88 patients with PI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were retrospectively studied, the clinical and pathological features, diagnosis and treatment process and prognosis of PI-DLBCL were analyzed, and univariate and multivariate analysis of prognostic factors was carried out. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of PI-DLBCL.ResultsAmong the 88 patients with PI-DLBCL included in this study, 60 cases were males (68.18%), 28 cases were females (31.82%), and 62 patients (70.45%) were complaining of abdominal pain, and the second most common clinical manifestation was changes in bowel habits in 16 (18.18%), with a median age of onset of 57 (17–82) years. The first-line treatment regimen was surgery combined with R-CHOP chemotherapy (56.82%). The median follow-up time was 72 (1–148) months, 51 (57.95%) of 88 patients with PI-DLBCL survived, 30 patients (34.09%) died, 7 patients (7.95%) were lost to follow-up, and the PFS rates of 1-year, 3-year and 5-year were 57.95%, 29.55% and 15.91%, and the OS rates of 1-year, 3-year and 5-year were 79.55%, 45.45% and 28.41%, respectively. The results of univariate Cox regression analysis showed that ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were the influencing factors of OS in PI-DLBCL patients, and ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were all the influencing factors of PFS in PI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.ConclusionPI-DLBCL is more common in middle-aged and elderly men, clinical manifestations lack specificity, first-line treatment is mainly surgery combined with standard chemotherapy regimens. The Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.

The global SARS-CoV-2 monitoring effort has been extensive, resulting in many states and countries establishing wastewater-based epidemiology programs to address the spread of the virus during the pandemic. Challenges for programs include concurrently optimizing methods, training new laboratories, and implementing successful surveillance programs that can rapidly translate results for public health, and policy making. Surveillance in Michigan early in the pandemic in 2020 highlights the importance of quality-controlled data and explores correlations with wastewater and clinical case data aggregated at the state level. The lessons learned and potential measures to improve public utilization of results are discussed.The Michigan Network for Environmental Health and Technology (MiNET) established a network of laboratories that partnered with local health departments, universities, wastewater treatment plants (WWTPs) and other stakeholders to monitor SARS-CoV-2 in wastewater at 214 sites in Michigan. MiNET consisted of nineteen laboratories, twenty-nine local health departments, 6 Native American tribes, and 60 WWTPs monitoring sites representing 45 % of Michigan's population from April 6 and December 29, 2020. Three result datasets were created based on quality control criteria. Wastewater results that met all quality assurance criteria (Dataset Mp) produced strongest correlations with reported clinical cases at 16 days lag (rho = 0.866, p < 0.05).The project demonstrated the ability to successfully track SARS-CoV-2 on a large, state-wide scale, particularly data that met the outlined quality criteria and provided an early warning of increasing COVID-19 cases. MiNET is currently poised to leverage its competency to complement public health surveillance networks through environmental monitoring for new and emerging pathogens of concern and provides a valuable resource to state and federal agencies to support future responses.

Cervical cancer is the second most prevalent malignancy affecting women’s health globally, and the number of morbidity and mortality from cervical cancer continues to rise worldwide. The 5-year survival rate of patients with recurrent or metastatic cervical cancer is significantly reduced, and existing treatment modalities have low efficacy and high adverse effects, so there is a strong need for new, effective, and well-tolerated therapies. Antibody-drug conjugates (ADCs) are a new targeted therapeutic modality that can efficiently kill tumor cells. This review aims to summarize the composition, research, and development history and mechanism of action of ADCs, to review the research progress of ADCs in the treatment of cervical cancer, and to summarize and prospect the application of ADCs.

Abstract Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single‐cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single‐cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell–cell signaling. In doing so, TB‐related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing. Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes, which respectively exhibit pro-inflammatory or anti-inflammatory functions. Therefore, modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing. Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity. In this study, we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures. The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages, thereby accelerating diabetic fracture healing. We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway. Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

Abstract Protein Phosphatase 4 Catalytic Subunit (PPP4C) is an evolutionarily conserved protein involved in multiple biological and pathological events, including embryogenesis, organogenesis, cellular homeostasis, and oncogenesis. However, the detailed mechanisms underlying these processes remain largely unknown. Thus, we investigated the potential correlation between PPP4C and biological processes (BPs) and canonical Wnt signaling using pan-cancer analysis and Xenopus laevis (X. laevis) embryo model. Our results indicate that PPP4C is a potential biomarker for specific cancer types due to its high diagnostic accuracy and significant prognostic correlation. Furthermore, in multiple cancer types, PPP4C-related differentially expressed genes (DEGs) were significantly enriched in pattern specification, morphogenesis, and canonical Wnt activation. Consistently, perturbation of Ppp4c in X. laevis embryos interfered with normal embryogenesis and canonical Wnt responses. Moreover, biochemical analysis of X. laevis embryos demonstrated that both endogenous and exogenous Ppp4c negatively regulated AXIN1 (Wnt inhibitor) abundance. This study provides novel insights into PPP4C roles in pattern specification and Wnt activation. The similarities in BPs and Wnt signaling regulation regarding PPP4C support the intrinsic link between tumorigenesis and early embryogenesis.

ObjectiveThis study aimed to investigate the promoting effect of a Bacillus velezensis (BV) strain on lactic acid bacteria (LAB) and determine its influence on the fermentation quality and aerobic stability of silage.MethodsFlat colony counting method was used to evaluate the effect of BV on the growth of LAB. Freshly harvested whole-plant corn was inoculated separately with BV and L. plantarum (LP), along with an uninoculated control group (CK), and assessed at 1, 3, 5, 7, 15, and 30 days of ensiling.ResultsThe results indicated that BV exhibited a proliferative effect on Weissella confusa, Lactobacillus plantarum L-2, and Pediococcus pentosaceus. And exhibited a more rapid pH reduction in BV-inoculated silage compared with that in CK and LP-inoculated silage during the initial stage of ensiling. Throughout ensiling, the BV and LP experimental groups showed enhanced silage fermentation quality over CK. Additionally, relative to LP-inoculated silage, BV-inoculated silage displayed reduced pH and propionic acid. BV also prolonged aerobic stability under aerobic conditions. The microbial community in BV-inoculated silage showed greater stability than that in LP-inoculated silage. Additionally, Firmicutes and Lactobacillus exhibited more rapid elevation initially in BV versus LP-inoculated silage, but reached comparable levels between the two inoculation groups in the later stage.ConclusionIn summary, BV enhanced the efficacy and aerobic stability of whole-plant corn silage fermentation by stimulating LAB proliferation.

Nanomedicine shows remarkable potential to improve the efficacy of diagnosis and treatment of tumors, utilizing nanotechnologies and nanomaterials. Gold nanoclusters (AuNCs) have emerged as a highly promising option due to their exceptional optical and enzyme‐mimicking catalytic activities as well as good biocompatibility. The renal clearable clusters can enrich in the tumors upon their enhanced permeability and retention properties, which benefits the tumor‐related applications. The fluorescence of AuNCs in the second near‐infrared region possesses extraordinary penetration depth and high temporal–spatial resolution, enabling excellent in vivo imaging and real‐time monitoring of pathological process. AuNC‐based nanoplatforms represent a paradigm of integrated, efficient, intelligent, and safe treatment strategy, extending personalized tumor therapy. Meanwhile, the optical and biocatalytic properties can be modulated by adopting the atom/ligand engineering, which further enhances the efficacy of AuNCs. Herein, the advances of AuNCs in the field of diagnosis and treatment of tumors are summarized and the directions to be improved are proposed to promote the clinical translation of the AuNCs.

AbstractObjective There is a paucity of research on the association between bile acids (BAs) levels and all-cause death in patients with diabetes mellitus (DM) on maintenance hemodialysis (MHD). This study aimed to investigate the clinical characteristics of patients with DM on MHD according to different BAs levels and their impact on prognosis.Methods A retrospective cohort of 1,081 patients on hemodialysis at Xindu People’s Hospital and the First Affiliated Hospital of Chengdu Medical College were enrolled. Demographic and clinical characteristics were collected. The relationship between BAs and all-cause death risk was fitted using restricted cubic splines (RCS), and the BAs cutoff value was calculated. Patients were divided into low and high BAs groups based on the cutoff value. The primary endpoint was all-cause death and the secondary outcomes were deaths from cardiovascular events.Results Finally, 387 patients with DM on MHD were included. The median BAs level of all patients was 4.0 μmol/L. The RCS-based BAs cutoff value was 3.5 μmol/L. The BAs levels correlated negatively with total cholesterol, low-density lipoprotein, and blood calcium levels. During the follow-up, 21.7% of the patients died. The multivariate Cox regression analysis demonstrated that patients with DM on MHD with higher BAs were associated independently with a decreased risk of all-cause death (HR =0.55; 95% CI, 0.35–0.81, p = 0.01) compared to those with lower BAs levels.Conclusions Higher BAs levels were associated with lower lipid levels in patients with DM on MHD. BAs is an independent risk factor for all-cause death in patients with DM on MHD.

Abstract. Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis-splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans-splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host–pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.

Plant essential oils have played an important role in the field of antibiotic alternatives because of their efficient bacteriostatic and fungistatic activity. As plant essential oils are widely used, their activity to improve the quality of plant silage has also been explored. This review expounds on the active ingredients of essential oils, their bacteriostatic and fungistatic activity, and mechanisms, as well as discusses the application of plant essential oils in plant silage fermentation, to provide a reference for the development and application of plant essential oils as silage additives in plant silage fermentation feed.

Abstract Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.

Objectives: How to choose proper lipoarabinomannan-testing assays for diagnosing tuberculosis (TB) in different populations baffles clinicians. This work assessed all reported lipoarabinomannan assays’ performance and aimed to identify the eligibility of each assay and offer guidance for clinicians. Methods: We searched PubMed, Embase, and Web of Science until August 23, 2020. The risk of bias was evaluated by QADAS-2. Heterogeneity was evaluated by the Cochran Q test and I2. Sensitivity and specificity were pooled by a bivariate mixed model (register number: CRD42021270506). Results: A total of 97 articles, covering 144 trials, 16 assays, 45,679 participants, and eight sample types, were divided into five groups. Electrochemiluminescence (ECL) had a sensitivity of 65%, specificity of 92%, and an area under curve (AUC) of 0.85 in diagnosing pulmonary TB in adults. ECL showed a promising diagnostic ability (sensitivity: 78%; specificity: 88%; AUC: 0.88) in patients with HIV, especially for urine detection (sensitivity: 90%; specificity: 89%; AUC: 0.95). The enzyme-linked immune assay showed a preference for diagnosing TB in Asians and Africans, especially in Africans who were smear-positive (sensitivity: 80%; specificity: 88%; AUC: 0.91). Conclusion: ECL was recommended for diagnosing pulmonary TB in adults, especially for TB/HIV co-infection. Taking urine as a sample further enhanced ECL's diagnostic performance. Enzyme-linked immune assay was recommended as an additional TB-related detection for smear-positive Africans.

Lactic acid bacteria (LAB) have the ability to ferment water-soluble carbohydrates, resulting in the production of significant amounts of lactic acid. When utilized as additives in silage fermentation and feed, they have been shown to enhance the quality of these products. Epiphytic LAB of plants play a major role in the fermentation of silage plants. Plant species in turn affect the community structure of epiphytic LAB. In recent years, an increasing number of studies have suggested that epiphytic LAB are more effective than exogenous LAB when applied to silage. Inoculating silage plants with epiphytic LAB has attracted extensive attention because of the potential to improve the fermentation quality of silages. This review discusses the interaction of epiphytic LAB with plants during silage fermentation and compares the effects of exogenous and epiphytic LAB on plant fermentation. Overall, this review provides insight into the potential benefits of using epiphytic LAB as an inoculant and proposes a theoretical basis for improving silage quality.

Abstract Background RNA secondary structure is very important for deciphering cell’s activity and disease occurrence. The first method which was used by the academics to predict this structure is biological experiment, But this method is too expensive, causing the promotion to be affected. Then, computing methods emerged, which has good efficiency and low cost. However, the accuracy of computing methods are not satisfactory. Many machine learning methods have also been applied to this area, but the accuracy has not improved significantly. Deep learning has matured and achieves great success in many areas such as computer vision and natural language processing. It uses neural network which is a kind of structure that has good functionality and versatility, but its effect is highly correlated with the quantity and quality of the data. At present, there is no model with high accuracy, low data dependence and high convenience in predicting RNA secondary structure. Results This paper designs a neural network called LTPConstraint to predict RNA secondary structure. The network is based on many network structure such as Bidirectional LSTM, Transformer and generator. It also uses transfer learning to train modelso that the data dependence can be reduced. Conclusions LTPConstraint has achieved high accuracy in RNA secondary structure prediction. Compared with the previous methods, the accuracy improves obviously both in predicting the structure with pseudoknot and the structure without pseudoknot. At the same time, LTPConstraint is easy to operate and can achieve result very quickly.

Abstract Background Abnormal glycosylation in a variety of cancer types is involved in tumor progression and chemoresistance. Glycosyltransferase C1GALT1, the key enzyme in conversion of Tn antigen to T antigen, is involved in both physiological and pathological conditions. However, the mechanisms of C1GALT1 in enhancing oncogenic phenotypes and its regulatory effects via non-coding RNA are unclear. Methods Abnormal expression of C1GALT1 and its products T antigen in human bladder cancer (BLCA) were evaluated with BLCA tissue, plasma samples and cell lines. Effects of C1GALT1 on migratory ability and proliferation were assessed in YTS-1 cells by transwell, CCK8 and colony formation assay in vitro and by mouse subcutaneous xenograft and trans-splenic metastasis models in vivo. Dysregulated circular RNAs (circRNAs) and microRNAs (miRNAs) were profiled in 3 pairs of bladder cancer tissues by RNA-seq. Effects of miR-1-3p and cHP1BP3 (circRNA derived from HP1BP3) on modulating C1GALT1 expression were investigated by target prediction program, correlation analysis and luciferase reporter assay. Functional roles of miR-1-3p and cHP1BP3 on migratory ability and proliferation in BLCA were also investigated by in vitro and in vivo experiments. Additionally, glycoproteomic analysis was employed to identify the target glycoproteins of C1GALT1. Results In this study, we demonstrated upregulation of C1GALT1 and its product T antigen in BLCA. C1GALT1 silencing suppressed migratory ability and proliferation of BLCA YTS-1 cells in vitro and in vivo. Subsets of circRNAs and miRNAs were dysregulated in BLCA tissues. miR-1-3p, which is reduced in BLCA tissues, inhibited transcription of C1GALT1 by binding directly to its 3′-untranslated region (3′-UTR). miR-1-3p overexpression resulted in decreased migratory ability and proliferation of YTS-1 cells. cHP1BP3 was upregulated in BLCA tissues, and served as an miR-1-3p “sponge”. cHP1BP3 was shown to modulate migratory ability, proliferation, and colony formation of YTS-1 cells, and displayed tumor-suppressing activity in BLCA. Target glycoproteins of C1GALT1, including integrins and MUC16, were identified. Conclusions This study reveals the pro-metastatic and proliferative function of upregulated glycosyltransferase C1GLAT1, and provides preliminary data on mechanisms underlying dysregulation of C1GALT1 via miR-1-3p / cHP1BP3 axis in BLCA.

Abstract Precision medicine applies machine learning methods to estimate the personalized optimal treatment decision based on individual information, such as genetic data and medical history. The main purpose of self obesity management is to develop a personalized optimal life plan that is easy to implement and adhere to, thereby reducing the incidence of obesity and obesity-related diseases. The methodology comprises three components. First, we apply catboost, random forest and lasso covariance test to evaluate the importance of individual features in forecasting body mass index. Second, we apply metaalgorithms to estimate the personalized optimal decision on alcohol, vegetable, high caloric food and daily water intake respectively for each individual. Third, we propose new metaalgorithms named SX and SXwint learners to compute the personalized optimal decision and compare their performances with other prevailing metalearners. We find that people who receive individualized optimal treatment options not only have lower obesity levels than others, but also have lower obesity levels than those who receive ’one-for-all’ treatment options. In conclusion, all metaalgorithms are effective at estimating the personalized optimal decision, where SXwint learner shows the best performance on daily water intake.

Background: Bone fracture healing is a postnatal regenerative process in which fibrocartilaginous callus formation and bony callus formation are important. Bony callus formation requires osteoblastic differentiation of MSCs. Materials and methods: The formation of callus was assessed by μCT, Safranin-O, H&E and Masson trichrome staining. Osteogenesis of MSCs was analyzed by ALP staining, ARS staining, qRT-PCR and WB. And we also used IF and TOP/FOP Flash luciferase reporter to assess the nuclear translocation of PP65. Results: In this study, we found Bcl-3 showed a significant correlation with bone fracture healing. Results of μCT showed that loss of Bcl-3 delays bone fracture healing. Safranin-O, H&E and Masson trichrome staining confirmed that loss of Bcl-3 impacted the formation of cartilage and woven bone in callus. Further experiments in vitro manifested that Bcl-3-knockdown could inhibit MSCs osteoblastic differentiation through releasing the inhibition on NF-κB signaling by Co-IP, IF staining and luciferase reporter assay. Conclusions: We unveiled that loss of Bcl-3 could lead to inhibited osteogenic differentiation of MSCs via promoting PP65 nuclear translocation. The translational potential of this article: Our data demonstrated that overexpression of Bcl-3 accelerates bone fracture healing, which serves as a promising therapeutic target for bone fracture treatment.

We systemically identified tuberculosis (TB)-related DNA methylation biomarkers and further constructed classifiers for TB diagnosis. TB-related DNA methylation datasets were searched through October 3, 2020. Limma and DMRcate were employed to identify differentially methylated probes (DMPs) and regions (DMRs). Machine learning methods were used to construct classifiers. The performance of the classifiers was evaluated in discovery datasets and a prospective independent cohort. Eighty-nine DMPs and 24 DMRs were identified based on 67 TB patients and 45 healthy controls from 4 datasets. Nine and three DMRs were selected by elastic net regression and logistic regression, respectively. Among the selected DMRs, two regions (chr3: 195635643–195636243 and chr6: 29691631–29692475) were differentially methylated in the independent cohort (p = 4.19 × 10−5 and 0.024, respectively). Among the ten classifiers, the 3-DMR logistic regression classifier exhibited the strongest performance. The sensitivity, specificity, and area under the curve were, respectively, 79.1%, 84.4%, and 0.888 in the discovery datasets and 64.5%, 90.3%, and 0.838 in the independent cohort. The differential diagnostic ability of this classifier was also assessed. Collectively, these data showed that DNA methylation might be a promising TB diagnostic biomarker. The 3-DMR logistic regression classifier is a potential clinical tool for TB diagnosis, and further validation is needed.

Obesity, a growing health problem in the world, is related to a series of mental disorders, including anxiety and depression. XiaoYao San (XYS), a prescription of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of anxiety and depression in China. However, the efficacy of XYS on obesity-related neuropsychiatric dysfunction and the underlying neural mechanisms remain unclear. Here, using a high-fat diet (HFD)-induced obese model, we found that XYS treatment significantly improves obesity-related anxiety- and depression-like behaviors and alters the gut microbiome, particularly by increasing the relative abundance of Faecalibaculum rodentium (F. rodentium), in mice. Interestingly, selective supplementation with F. rodentium or its metabolic products, short-chain fatty acids (SCFAs), is sufficient to rescue anxiety- and depression-like behaviors in HFD-fed mice. Next, we determined that the transcriptional level of dopamine D2 receptor (DRD2), which activation usually inhibits inflammation in the central nervous system (CNS), is significantly increased in the medial prefrontal cortex (mPFC) of XYS-treated mice when compared with that of vehicle-treated controls. Moreover, enriched pathways analysis with the differential expression genes (DEGs) showed that some of these DEGs are enriched in neuroinflammatory pathways. We further noticed that treatment with XYS contributes to controlling microglial activation and proinflammatory responses in the mPFC and hippocampus of HFD-fed mice. Overall, this study reveals that XYS rescues HFD-induced anxiety and depression via modulating gut microbiota-derived metabolites and that XYS is a potential therapeutic strategy for treating obesity-associated mental disorders.

Abstract Finding a suitable biomaterial for scaffolding in cartilage tissue engineering has proved to be far from trivial. Nonetheless, it is clear that biomimetic approaches based on gelatin (Gel) and hyaluronic acid (HA) have particular promise. Herein, a set of formulations consisting of photo-polymerizable Gel; photo-polymerizable HA, and allogenic decellularized cartilage matrix (DCM), is synthesized and characterized. The novelty of this study lies particularly in the choice of DCM, which was harvested from an abnormal porcine with α-1,3-galactose gene knockout. The hybrid hydrogels were prepared and studied extensively, by spectroscopic methods, for their capacity to imbibe water, for their behavior under compression, and to characterize microstructure. Subsequently, the effects of the hydrogels on contacting cells (in vitro) were studied, i.e., cytotoxicity, morphology, and differentiation through monitoring the specific markers ACAN, Sox9, Coll2, and Col2α1, hypertrophy through monitoring the specific markers alkaline phosphatase (ALP) and Col 10A1. In vivo performance of the hydrogels was assessed in a rat knee cartilage defect model. The new data expand our understanding of hydrogels built of Gel and HA, since they reveal that a significant augmenting role can be played by DCM. The data strongly suggest that further experimentation in larger cartilage-defect animal models is worthwhile and has potential utility for tissue engineering and regenerative medicine.

ObjectiveDiarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the ex vivo interactions of SJZD and IBS-D’s intestinal microbiota.MethodsFive samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37°C for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3/V4 regions and a nontargeted metabolome platform, respectively.ResultsAfter being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergistic pattern of neurotransmitter metabolism between Streptococcus and E. Shigella.ConclusionSJZD rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D’s major symptoms.

Introduction To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC). Material and methods The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40. Results The TLS distribution was significantly higher in the tumor invasive edge than the tumor center (p < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients. Conclusions We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.

Tumor infiltration pattern (INF) and tumor origin site were reported to significantly affect the prognosis of gastric cancer (GC), while the immune status under these contexts is not clear. In this study, we correlated the density and phenotype of tumor-infiltrating lymphocytes (TILs) with INF and the tumor origin site to reflect the biological behavior of tumors from a new perspective and also determined their effects on overall survival (OS) and other related clinicopathological features in archival samples of 147 gastric cancers with 10-year follow-up data. We found that the INFc growth pattern (an invasive growth without a distinct border) of GC lacked immune cell infiltration, particularly the cytotoxic T cells and their activated form. It is also significantly associated with an unfavorable prognosis (P < 0.001) and proximal site (P = 0.001), positive lymph node metastasis (P = 0.002), and later tumor–node–metastasis stage (P < 0.001). Moreover, the density and sub-type of TILs infiltration were significantly different in disparate differentiated areas for the tumor tissue with INFb. Compared with distal gastric cancer, proximal gastric cancers were prone to grow in an INFc pattern (P = 0.001) and infiltrated with fewer TILs, experiencing a shorter survival time (P = 0.013). Multivariate analysis showed that only the INF and the density of TILs were demonstrated to be the independent prognostic factors of OS for the GC. We concluded that GC with an aggressive growth pattern arising from proximal sites always had a weak immune response and resulted in a poor prognosis. The interaction between them and their synergistic or antagonistic effects in the development of tumors need to be further studied. This study opens up a new perspective for research on the biological behavior of the tumor.

The Zn-ion micro-supercapacitor (ZMSC) is a promising candidate for developing miniaturized and integrated energy storage devices. To achieve high-performance functional groups with simple processing to composite with rod-like active PANI fibers, we prepared exfoliated graphene (EG) with an appropriate amount of O-containing functional groups. The appropriate O content simultaneously facilitated self-assembly of the EG and PANI fibers and maintained the electric conductivity of the composite, producing a free-standing EG/PANI film without additional conductive additives or current collectors. As an interdigital electrode for the ZMSC, the EG/PANI film showed ultrahigh capacitance of 1.8 F cm−2 at 2.6 mA cm−2 (361.3 F g−1 at 0.5 A g−1) and landmark energy density of 755.8 μWh cm−2 at 2.3 mW cm−2 (148.2 Wh kg−1 at 451.7 W kg−1). The facile preparation of the high-performance EG/PANI electrode provides a potential path for practical applications with ZMSCs.

Abstract Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.

Abstract Background Osteosarcoma (OS) is a common severe illness globally. Lupeol has been reported to participate in the pathophysiologic properties of various cancers, including OS. This study aimed to explore the effects of lupeol on proliferation, invasion, and apoptosis on OS cells and the underlying mechanism. Methods The cell viability of OS cells was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The expression levels of miR-212-3p and high-mobility group AT-hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS cells. The cell apoptosis and invasion were detected by flow cytometry and transwell invasion assays, respectively. The functional target of miR-212-3p was predicted by online software and confirmed by luciferase reporter assay. The protein level of HMGA2 was measured by western blot analysis. Results Lupeol suppressed cell viability and invasion, and promoted apoptosis by upregulating the expression of miR-212-3p in OS cells. Knockdown of miR-212-3p restored the anti-tumor effect of lupeol. Interestingly, miR-212-3p directly targeted HMGA2 and suppressed its expression. Moreover, HMGA2 reversed the inhibited impact on viability and invasion, and the promoted effect on apoptosis induced by upregulation of miR-212-3p. Also, lupeol administration exerts its anti-tumor effect by overexpression of miR-212-3p to suppress the expression of HMGA2 in OS cells. Conclusion Lupeol inhibited OS progression by modulating the miR-212-3p/HMGA2 axis in vitro.

Gastric cancer (GC) is rampant around the world. Most of the GC cases are detected in advanced stages with poor prognosis. The identification of marker genes for early diagnosis is of great significance. Studying the tumor environment is helpful to acknowledge the process of tumorigenesis, development, and metastasis. Twenty-two kinds of immune cells were calculated by CIBERSORT from Gene Expression Omnibus (GEO) database. Subsequently, higher infiltration of macrophages M0 was discovered in GC compared with normal tissues. WGCNA was utilized to construct the network and then identify key modules and genes related to macrophages in TCGA. Finally, 18 hub genes were verified. In the PPI bar chart, the top 3 genes were chosen as hub genes involved in most pathways. On the TIMER and THPA websites, it is verified that the expression levels of CYBB, CD86, and C3AR1 genes in tumor tissues were higher than those in normal tissues. These genes may work as biomarkers or targets for accurate diagnosis and treatment of GC in the future. Our findings may be a new strategy for the treatment of GC.

A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., in vitro biocompatibility was assessed by the CCK-8 and live–dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the in vivo performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.

Twitter has become a major social media platform and has attracted considerable interest among researchers in sentiment analysis. Research into Twitter Sentiment Analysis (TSA) is an active subfield of text mining. TSA refers to the use of computers to process the subjective nature of Twitter data, including its opinions and sentiments. In this research, a thorough review of the most recent developments in this area, and a wide range of newly proposed algorithms and applications are explored. Each publication is arranged into a category based on its significance to a particular type of TSA method. The purpose of this survey is to provide a concise, nearly comprehensive overview of TSA techniques and related fields. The primary contributions of the survey are the detailed classifications of numerous recent articles and the depiction of the current direction of research in the field of TSA.

Fluctuation ('noise') in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet the mechanisms behind large fluctuations that are induced by single transcriptional activators remain elusive. Here, we probed putative mechanisms by studying the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, chromatin accessibility, and levels of mRNAs and proteins in single cells. Using a light-induced expression system, we showed that the transcriptional activator could form an interplay with dual functional co-activator/histone acetyltransferases CBP/p300. This interplay resulted in substantial heterogeneity in H3K27ac, chromatin accessibility, and transcription. Simultaneous attenuation of CBP/p300 and HDAC4/5 reduced heterogeneity in the expression of endogenous genes, suggesting that this mechanism is universal. We further found that the noise was reduced by pulse-wide modulation of transcriptional activator binding possibly as a result of alternating the epigenetic states. Our findings suggest a mechanism for the modulation of noise in synthetic and endogenous gene expression systems.

Teriparatide, also known as 1-34 parathyroid hormone (PTH (1-34)), is commonly used for the treatment of osteoporosis in postmenopausal women. But its therapeutic application is restricted by poor metabolic stability, low bioavailability, and rapid clearance. Herein, PTHG2, a glycosylated teriparatide derivative, is designed and synthesized to improve PTH stability and exert more potent antiosteoporosis effect. Surface plasmon resonance (SPR) analysis shows that PTHG2 combines to PTH 1 receptor. Additional acetylglucosamine covalent bonding in the first serine at the N terminal of PTH (1-34) improves stability and increases protein hydrolysis resistance. Intermittent administration of PTHG2 preserves bone quality in ovariectomy- (OVX-) induced osteoporosis mice model, along with increased osteoblastic differentiation and bone formation, and reduced marrow adipogenesis. In vitro, PTHG2 inhibits adipogenic differentiation and promotes osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs). For molecular mechanism, PTHG2 directs BMSCs fate through stimulating the cAMP-PKA signaling pathway. Blocking PKA abrogates the pro-osteogenic effect of PTHG2. In conclusion, our study reveals that PTHG2 can accelerate osteogenic differentiation of BMSCs and inhibit adipogenic differentiation of BMSCs and show a better protective effect than PTH (1-34) in the treatment of osteoporosis.

Accurate RNA secondary structure information is the cornerstone of gene function research and RNA tertiary structure prediction. However, most traditional RNA secondary structure prediction algorithms are based on the dynamic programming (DP) algorithm, according to the minimum free energy theory, with both hard and soft constraints. The accuracy is particularly dependent on the accuracy of soft constraints (from experimental data like chemical and enzyme detection). With the elongation of the RNA sequence, the time complexity of DP-based algorithms will increase geometrically, as a result, they are not good at coping with relatively long sequences. Furthermore, due to the complexity of the pseudoknots structure, the secondary structure prediction method, based on traditional algorithms, has great defects which cannot predict the secondary structure with pseudoknots well. Therefore, few algorithms have been available for pseudoknots prediction in the past. The ATTfold algorithm proposed in this article is a deep learning algorithm based on an attention mechanism. It analyzes the global information of the RNA sequence via the characteristics of the attention mechanism, focuses on the correlation between paired bases, and solves the problem of long sequence prediction. Moreover, this algorithm also extracts the effective multi-dimensional features from a great number of RNA sequences and structure information, by combining the exclusive hard constraints of RNA secondary structure. Hence, it accurately determines the pairing position of each base, and obtains the real and effective RNA secondary structure, including pseudoknots. Finally, after training the ATTfold algorithm model through tens of thousands of RNA sequences and their real secondary structures, this algorithm was compared with four classic RNA secondary structure prediction algorithms. The results show that our algorithm significantly outperforms others and more accurately showed the secondary structure of RNA. As the data in RNA sequence databases increase, our deep learning-based algorithm will have superior performance. In the future, this kind of algorithm will be more indispensable.

Different modification process routes are used to improve the modified cellulose nanocrystalline (MCNC) with higher fatty acid by esterification reaction and graft polymerization to obtain certain hydrophobic properties. Two preparation methods, product structure and surface activity, are compared and explored. Experimental results show that the modified product is still at the nanometer level and basically retains the crystal structure of the raw cellulose nanocrystalline (CNC). The energy consumption of the two preparation methods is low; however, the esterification method with co-reactant requires short reaction time, and the degree of substitution of the product is high. The modified product prepared by grafting polymerization method has a high HLB value and amphiphilicity, which can effectively reduce the surface tension of water. Therefore, it can be used as a green and environmentally friendly surface-active substance.

Procrastination tendencies are prevalent and are associated with negative psychosocial outcomes. However, how preservice teachers' procrastination tendencies prior to the COVID-19 pandemic link to their experiences during and after the COVID-19 pandemic have not been investigated. The present study collected data from three time points, examining how preservice teachers' procrastination tendencies before the COVID-19 pandemic related to their life satisfaction at the beginning of the COVID-19 pandemic, and their perceived work stress and the COVID-19 impact two and a half years after the outbreak of the pandemic. A total of 385 preservice teachers from Hong Kong were included in this study. Results from structural equation modeling revealed that preservice teachers' higher procrastination tendencies before the COVID-19 pandemic were associated with lower life satisfaction at the start of the COVID-19 pandemic, which in turn was linked to higher perceived work stress and a more severe COVID-19 impact two and a half years after the COVID-19 outbreak. The results indicated that preservice teachers with procrastination tendencies may be especially vulnerable to experiencing work stress and life disruption in the face of traumatic events or crises. The findings provide valuable insights to both researchers and practitioners, highlighting the importance of addressing procrastination tendencies among preservice teachers.

Vital signs monitoring in physical activity (PA) is of great significance in daily healthcare. Impulse Radio Ultra-WideBand (IR-UWB) radar provides a contactless vital signs detection approach with advantages in range resolution and penetration. Several researches have verified the feasibility of IR-UWB radar monitoring when the target keeps still. However, various body movements are induced by PA, which lead to severe signal distortion and interfere vital signs extraction. To address this challenge, a novel joint chest–abdomen cardiopulmonary signal estimation approach is proposed to detect breath and heartbeat simultaneously using IR-UWB radars. The movements of target chest and abdomen are detected by two IR-UWB radars, respectively. Considering the signal overlapping of vital signs and body motion artifacts, Empirical Wavelet Transform (EWT) is applied on received radar signals to remove clutter and mitigate movement interference. Moreover, improved EWT with frequency segmentation refinement is applied on each radar to decompose vital signals of target chest and abdomen to vital sign-related sub-signals, respectively. After that, based on the thoracoabdominal movement correlation, cross-correlation functions are calculated among chest and abdomen sub-signals to estimate breath and heartbeat. The experiments are conducted under three kinds of PA situations and two general body movements, the results of which indicate the effectiveness and superiority of the proposed approach.

Although a secondary mutation and the epithelial-to-mesenchymal transition (EMT) are encountered very often in patients received the EGFR-TKI targeted treatment. The entire detrimental morphological change of the cancer entity was rare reported. Herein we report a case that acquired resistance to EGFR-TKI with T790M mutation and complete EMT morphological change of the tumor tissue. The primary lung tumor from a 52-year-old woman was diagnosed with moderate differentiated adenocarcinoma, with intensively positiveTTF-1 and E-cadherin in differentiated glandular structure but not the budding cancer cell cluster which with an intensive Vimentin staining. Molecular analysis revealed an EGFR exon 19 deletion and with an excellent response to Gefitinib treatment. Microscopic examination of recurred tumor specimens revealed a diffuse poorer differentiated proliferation of atypical cells. Immunostaining showed intensive Vimentin but almost completely negative for E-cadherin and TTF-1. Genetic analyses revealed T790M mutation. It is worth noting that rare clinical studies have been reported that acquired EGFR-TKI resistant lung adenocarcinoma underwent T790M mutation and almost complete EMT together. More significantly, the similarity of poorly differentiated cancer cell cluster in the primary lesions to recurred tumor lesions, which may pre-harbor drug resistance mutation should not be neglected underneath the predominant morphologic patterns.

There is concern over social and emotional skill development in early childhood settings. The aim of this systematic observational study was to examine children’s prosocial and problem behaviors in small group settings. Especially, we studied how gender and closeness of friendships influence on children’s group level behavior. Altogether, nine video recordings were coded to observe peer interactions among children during tablet game sessions, where all 15 participants, aged 5 and 6 years, were allocated into four-member groups. The recordings were coded with a modified version of the Social Skills Improvement System Rating Scale. Social network analysis was employed to analyze the density and centrality of the interactions. Our results showed a wide variety of frequencies in different behaviors. In all, prosocial behavior was four times more typical than problem behavior, and there were more initiating than responding behaviors. Unlike prosocial behaviors, which were often verbal, most problem behaviors were nonverbal. The children interacted more actively with their best friends, and boys contributed more to both prosocial and problem behaviors than girls. A practical and concise peer interaction observation tool (PIOT) was developed for this study that can be used to follow children’s social and emotional skills in peer interactions.

The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites) to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015) [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number http://www.ebi.ac.uk/pride/archive/projects/PXD002265. Keywords: Matrix metalloproteinases, MMPs, PICS, Proteomics, Quenched fluorescence, Specificity profiling, Cleavage sites

Background/Aims: Several studies have reported that tumor-derived exosomes contain kinds of miRNAs, including oncogenic miRNAs and tumor suppressor miRNAs. It has been reported that miR-302b could inhibit cancer progression by targeting oncogenes post-transcriptionally. Whether miR-302b is involved in the regulation of tumor-derived exosomes on lung cancer cells proliferation has not yet been demonstrated. This study aimed to examine the effect of exosomes-derived miR-302b on lung cancer cells proliferation and explain the potential mechanism. Methods: The effect of exosomes derived from 95C cells and 95D cells with different metastatic ability on lung cancer cell proliferation and migration were analyzed by MTT assay and Transwell assays, respectively. Exosomes of 95C and 95D cells derived miR-302b was quantified by qRT-PCR, the effect of miR-302b on proliferation and migration of 95D cells was analyzed by MTT assays and Transwell assays respectively after transfection with miR-302b, while the expression of phosphorylated ERK1/2, MMP9 and TGFβRⅡ was analyzed by Western blot. The target gene of miRNA-302b was analyzed by Luciferase reporter assays. Results: 95C-derived exosomes significantly decreased the migration ability of 95D cells. miRNA-302b was significantly overexpressed in 95C cells and 95C-derived exosomes compared with 95D cells and 95D-derived exosomes. Transfection of miR-302b into 95D cells significantly suppressed cells proliferation and migration capabilities along with the down-regulated expression of TGFβRII, phosphorylated ERK1/2 and MMP9 induced by TGF-β1. Conclusions: Exosomes-derived miR-302b could suppress lung cancer cell proliferation and migration via the TGFβRII/ERK pathway and thus provides a potential target for human lung cancer therapy.

The rapid growth in social networking services has led to the generation of a massivevolume of opinionated information in the form of electronic text. As a result, the research on textsentiment analysis has drawn a great deal of interest. In this paper a novel feature weighting approachis proposed for the sentiment analysis of Twitter data. It properly measures the relative significanceof each feature regarding both intra-category and intra-category distribution. A new statistical modelcalled Category Discriminative Strength is introduced to characterize the discriminability of thefeatures among various categories, and a modified Chi-square (2)-based measure is employed tomeasure the intra-category dependency of the features. Moreover, a fine-grained feature clusteringstrategy is proposed to maximize the accuracy of the analysis. Extensive experiments demonstrate thatthe proposed approach significantly outperforms four state-of-the-art sentiment analysis techniquesin terms of accuracy, precision, recall, and F1 measure with various sizes and patterns of training andtest datasets.

In order to solve the problem of automatic evaluation of dispatcher fault simulation training in distribution network, a simulation training evaluation method based on radar chart for distribution network fault is proposed. The fault handling information matrix is established to record the dispatcher fault handling operation sequence and operation information. The four situations of the dispatcher fault isolation operation are analyzed. The fault handling anti-misoperation rule set is established to describe the rules prohibiting dispatcher operation. Based on the idea of artificial intelligence reasoning, the feasibility of dispatcher fault handling is described by the feasibility index. The relevant factors and evaluation methods are discussed from the three aspects of the fault handling result feasibility, the anti-misoperation correctness and the operation process conciseness. The detailed calculation formula is given. Combining the independence and correlation between the three evaluation angles, a comprehensive evaluation method of distribution network fault simulation training based on radar chart is proposed. The method can comprehensively reflect the fault handling process of dispatchers, and comprehensively evaluate the fault handling process from various angles, which has good practical value.

PO4(3-) and SiO3(2-) are often used as modifier to improve stability and aggregating ability of the iron-base coagulants, however, there are few reports about their detailed comparison between the coagulation performance and mechanisms. In this study, three coagulants--polyferric phosphoric sulfate (PFPS), polysilicon ferric sulfate (PFSS), and polyferric sulfate (PFS) were synthesized; their structure and morphology were characterized by Fourier transformed infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and Scanning electron microscope (SEM). Alkali titration and Ferron species analysis were employed to investigate the hydrolysis performance and species distribution. Jar test was conducted to measure their coagulation behaviors at different dosage, pH, and temperatures in which the flocs properties were measured. The results showed that a number of new compounds were formed due to the presence of PO4(3-) and SiO3(2-). Moreover, PFPS and PFSS had similar level in Fea as well as Feb. Among them, PFPS produced more multi-core iron atoms polymer and content of Feb, and the formed flocs were larger and denser. It exhibited superior coagulation performance in terms of turbidity reduction, UV254 removal and residual ferric concentration. Jar test and floc breakage/regrowth experiments indicated other than charge neutrality, the dominated mechanism involved in PFSS was the adsorption between polysilicic acid and solution particle, while PFPS was sweeping, entrapment/adsorption resulting from larger polymer colloid of Fe-P chemistry bond.